Immunologic Research[JOURNAL]
Sun
200 papers
Dysautonomia as a form of presentation of primary Sjögren's disease: a case series of six patients.
Godínez-Lazarini E, Cimé-Aké E, Peña-Ojeda M … +4 more , Ríos-Valencia J, Faz-Muñoz D, Hernández-Molina G, Fragoso-Loyo H
Immunol Res · 2025 Sep · PMID 40911106 · Publisher ↗
We present six patients with dysautonomia secondary to primary Sjögren's disease (pSjD) and analyze the literature regarding this topic. Case series. Patients were retrospectively recruited from a tertiary center in Mexi...
We present six patients with dysautonomia secondary to primary Sjögren's disease (pSjD) and analyze the literature regarding this topic. Case series. Patients were retrospectively recruited from a tertiary center in Mexico from 2001 to 2022 and included if they met 2016 ACR/EULAR criteria for SjD. Dysautonomia was diagnosed by the presence of autonomic symptoms and at least one of Ewin's battery tests. We scored the Composite Autonomic Severity Scale (CASS), and the Composite Autonomic Symptom Score (COMPASS-31). Patients (n = 6) were primarily females (83%), with a range of 23 to 60 years at onset of neurological manifestations. Dysautonomia preceded 2-10 years the diagnosis of pSjD in five patients. The clinical manifestations varied, but all patients had orthostatic hypotension and syncope. Patients had variability regarding non-neurological disease activity (ESSDAI 0-15) at the onset of neurological manifestations. Treatment for dysautonomia included prednisone, hydroxychloroquine, DMARDs, rituximab, or their combinations. Overall, we observed partial improvement in most of the cases and only one patient had remission of her symptoms of dysautonomia. Two patients discontinued treatment and lost follow-up. Few cases of dysautonomia and biopsy proven pSjD were identified in the literature, but they shared clinical features with ours. Dysautonomia is a rare and challenging neurological manifestation attributed with pSjD. The main symptoms in our patients were orthostatic hypotension and syncope; and most of the times preceded SjD diagnosis. Partial improvement was achieved in the majority of patients following treatment.
Development of an in vitro method to assess the immunogenicity of biologics in the prevention of infectious diseases.
Baran J, Kuryk Ł, Garofalo M … +8 more , Prygiel M, Zasada A, Szczepińska T, Staniszewska A, Kala D, Majewski P, Charkiewicz R, Staniszewska M
Immunol Res · 2025 Sep · PMID 40900356 · Full text
We present a series of preclinical studies focused on developing in vitro 2D and 3D models for assessing immunogenic factors in preventing infectious diseases. Human peripheral blood mononuclear cells (PBMC) and Calu-3 c...
We present a series of preclinical studies focused on developing in vitro 2D and 3D models for assessing immunogenic factors in preventing infectious diseases. Human peripheral blood mononuclear cells (PBMC) and Calu-3 cell lines (bronchial epithelial cells) were used to develop 2D and 3D models. Peptides: Spike-S1-His (S-His), nucleocapsid-His and adjuvants: human adenovirus five serotype-based viral vector (AdV-D24-ICOSL-CD40L), armed with inducible co-stimulator (ICOSL) and CD40 ligand (CD40L), and a vector lacking these transgenes (AdV5/3) were used due to their effective initial interaction with antigen-presenting cells (APC). Studying the potency of biologics in vitro revealed a significant increase in the percentage of CD4 TCM, CD4 TEMRA, and CD4 TEM lymphocyte subpopulations involved in memory cell generation after 24 h of treatment. Prolonging the exposure for 7 days, a significant increase in CD4 cells was observed when PBMCs were treated with AdV1 (56.00 ± 0.26% vs. 48.17 ± 1.10%). In contrast, a decrease in CD8 cells was observed in those treated with AdV1 (37.93 ± 0.35%) compared to AdV1 + S-His + N-His (38.47 ± 0.38%) versus the untreated group (44.63 ± 1.07%). A decrease in EMRA was noted when PBMCs were treated with AdV1 + S-His + N-His (2.97 ± 0.23% vs. 4.50 ± 0.35%). Moreover, it was pointed out that PBMCs treated with AdV1 alone or in combination with S-His and N-His showed an elevated number of naïve CD4/CD8 and SCM CD4/CD8 cells. No changes in the number of EMRA CD4 subpopulations were detected when PBMCs were treated with AdV2 compared with untreated ones (4.27 ± 0.06% vs. 4.50 ± 0.35%). Analysis of the humoral response induced by AdV1, AdV2, S-His, N-His, AdV1 + S-His + N-His, and AdV2 + S-His + N-His showed that AdV1 alone (4.17 ± 0.25% vs. 3.17 ± 0.06%) and in combination with S-His and N-His (3.87 ± 0.25 vs. 3.17 ± 0.06%) slightly increased the number of CD19 cells. RNA-Seq analysis of PBMC cells in the 3D model revealed gene overexpression, including FGFR4, associated with the Rap1 pathway in samples exposed to AdV1 + S-His + N-His. Thus, the proposed platform's impact on lymphocyte differentiation was confirmed, and cytokine profile analysis in this sample revealed elevated levels of IL-10, IL-12p70, and IL-8. All samples exposed to AdV showed increased levels of IFN-γ. The safety and biodistribution studies of the vaccine platform demonstrated that a 30-day exposure did not impact mice's survival or organ morphology. Exploring the CD40 pathway notably reveals its significant impact on immune cell populations, suggesting potential therapeutic avenues.
Sex-related differences in cell-free DNA and neutrophil extracellular traps in patients with hematologic malignancies.
Gnecco G, Davini A, Valeriano A … +6 more , Mancuso P, Derenzini E, Lamorte G, Prati D, Talarico G, Bertolini F
Immunol Res · 2025 Aug · PMID 40856921 · Full text
Cell-free DNA (cfDNA) is emerging as a promising biomarker in liquid biopsy applications for cancer, with growing interest in its potential utility also for the diagnosis, monitoring of treatment response, and detection...
Cell-free DNA (cfDNA) is emerging as a promising biomarker in liquid biopsy applications for cancer, with growing interest in its potential utility also for the diagnosis, monitoring of treatment response, and detection of relapse in hematologic malignancies. However, the precise origin and clinical relevance of cfDNA in these disorders remain to be fully clarified. In this study, we analyzed plasma samples from 98 patients with hematologic malignancies and 80 healthy donors using quantitative PCR (qPCR) to quantify cfDNA concentrations. We further examined associations between cfDNA levels and clinical parameters, including sex and measurable residual disease (MRD). Our results demonstrated significantly elevated cfDNA levels in patients compared to healthy individuals, with a strong correlation between cfDNA concentration and presence/MRD of the disease. We also identified sex-specific differences in cfDNA levels. Notably, our findings suggest that neutrophils, through the release and degradation of neutrophil extracellular traps (NETs), may constitute a relevant source of circulating cfDNA. In addition, cfDNA concentrations were significantly associated with MRD status, supporting the potential role of cfDNA as a non-invasive biomarker for disease monitoring. Overall, our data highlight the clinical relevance of cfDNA in hematologic malignancies, both as a surrogate for disease burden and as a possible player in disease pathophysiology, thus offering a promising avenue for improved diagnostic and therapeutic strategies.
A nasal vaccine candidate based on S2 and N proteins from SARS-CoV-2 generates a broad antibody response systemically and in the lower respiratory tract.
Lobaina Y, Chen R, Vazquez-Blomquist D … +8 more , Suzarte E, Zhang M, Zhou Z, Lan Y, Guillen G, Li W, Perera Y, Hermida L
Immunol Res · 2025 Aug · PMID 40859051 · Publisher ↗
Since the beginning of the COVID-19 pandemic, various groups around the world have intensively worked in the development of vaccine candidates against SARS-CoV-2. Several vaccines have been approved in the past years; th...
Since the beginning of the COVID-19 pandemic, various groups around the world have intensively worked in the development of vaccine candidates against SARS-CoV-2. Several vaccines have been approved in the past years; the majority is based on the Spike or RBD proteins and employs parenteral administration routes. Considering the recent history of coronavirus zoonotic events, which are known to have caused serious human health problems, the development of vaccines with a broad scope of protection and the potential to cut/reduce the transmission remains in the spotlight. The current global pandemic preparedness initiatives have also promoted the preclinical evaluation of a new group of coronavirus vaccines. In line with current needs, the goal of the present work is the preclinical evaluation, in two different mice strains, of a novel nasal vaccine candidate based on two highly conserved sarbecovirus proteins, S2 and nucleocapsid (N). The vaccine preparation, containing a CpG ODN as adjuvant, was able to generate high antibody titers against both antigens, in sera and bronchoalveolar lavages. This humoral response results cross-reactive to SARS-CoV-1 and MERS-CoV. In addition, the preparation induces IFNγ secretion, and a marked IgG2a response, against both proteins at the systemic compartment, consistent with the development of a Th1 pattern. Although further evaluations should be done, the level of cross-reactivity and the mucosal response obtained constitute promising features of this vaccine candidate.
Mitochondrial sirtuins 3, 4 and 5 in patients with psoriasis.
Matuszyńska M, Poniewierska-Baran A, Duchnik E … +3 more , Marchlewicz M, Pawlik A, Słuczanowska-Głąbowska S
Immunol Res · 2025 Aug · PMID 40850958 · Publisher ↗
Psoriasis is one of the most common chronic inflammatory skin diseases and is characterised by the uncontrolled proliferation of keratinocytes and their abnormal differentiation. Sirtuins are a group of enzymes that play...
Psoriasis is one of the most common chronic inflammatory skin diseases and is characterised by the uncontrolled proliferation of keratinocytes and their abnormal differentiation. Sirtuins are a group of enzymes that play an important role in post-translational modifications of proteins, such as deacetylation, poly-ADP-ribosylation, demalonylation and lipoamidation. They are found in various cell types and are involved in ribosomal DNA recombination, gene silencing and DNA repair. This study aimed to examine the plasma levels of sirtuin 3, 4 and 5 in patients with psoriasis and correlate these levels with clinical parameters. The study included 43 patients with plaque-type psoriasis and 28 healthy controls. The plasma concentrations of sirtuin 3 were statistically significantly increased in patients with psoriasis compared to the control subjects. The plasma concentrations of sirtuin 4 and 5 were statistically significantly lower in patients with psoriasis than in the control group. No statistically significant correlations were found between the plasma levels of sirtuin 3 and 4 and the psoriasis activity tools of PASI, DLQI and the BSA index or the selected clinical parameters in patients with psoriasis. Plasma concentrations of sirtuin 5 correlated statistically significantly with the BSA index, haemoglobin and leukocytes. The results of this study suggest the involvement of sirtuin 3, 4 and 5 in the pathogenesis of psoriasis. However, an explanation of the role of sirtuins in psoriasis requires further research.
Dissecting the heterogeneity and tumor-associated dynamics of human liver group I ILC via scRNA sequencing data.
Zhang Y, He J, Li X … +4 more , Han Z, Chen H, Yang Z, Wang Y
Immunol Res · 2025 Aug · PMID 40848166 · Publisher ↗
Single-cell transcriptome analysis has made outstanding contributions to the identification of new cell lineages and the study of cancer immune microenvironment. Yet, the characterization of human liver type 1 innate lym...
Single-cell transcriptome analysis has made outstanding contributions to the identification of new cell lineages and the study of cancer immune microenvironment. Yet, the characterization of human liver type 1 innate lymphoid cells (ILC1s) and their dynamic changes in the tumor microenvironment have not been thoroughly studied at this detailed level. Here, we performed an integrated analysis of mouse and human liver immune cells to identify human liver ILC1s based on identified mouse liver ILC1s and to verify its functional similarity. Additionally, our findings highlighted the different expression patterns of the transcription factor EOMES in human versus mouse liver ILC1s, suggesting its reduced regulatory significance in human liver nature killer (NK) cells and ILC1s compared to murine models. A unique subset of intermediate innate lymphoid cells (intILCs) was identified, exhibiting traits of both human liver NK cells and ILC1s. Single-cell RNA sequencing (scRNA-seq) data analysis and TCGA dataset were utilized to characterize the distinct alterations in the genes and functions of NK cells, ILC1s, and intILCs in human hepatocellular carcinoma (HCC). It was found that the dynamic changes of liver ILC1s and intILCs, along with some of their subpopulations, may be key factors in tumor progression. This study provided new insights into the identification of ILC1s in human liver and the immunologic changes and mechanism of innate lymphoid cells (ILCs) in the tumor microenvironment, and these findings may be applicable to improving the diagnosis and treatment of hepatocellular carcinoma.
Targeting epigenetic modifications as an emerging immunotherapeutic strategy for cancers.
Kumar RI, Jain K, Rai KR … +2 more , Gururajan H, Sarkar K
Immunol Res · 2025 Aug · PMID 40830733 · Publisher ↗
The field of epigenetics has significantly advanced our understanding of gene regulation in cancer, revealing dynamic modifications that do not alter the DNA sequence yet profoundly influence gene expression. These inclu...
The field of epigenetics has significantly advanced our understanding of gene regulation in cancer, revealing dynamic modifications that do not alter the DNA sequence yet profoundly influence gene expression. These include DNA methylation, histone modifications, non-coding RNAs, chromatin remodeling, and RNA modifications. In malignancies such as colorectal, breast, lung, glioblastoma, and hematologic cancers, these epigenetic alterations contribute to tumor initiation, progression, and immune evasion. Emerging evidence reveals that such modifications shape the tumor-immune interface by influencing antigen presentation, immune cell infiltration, and cytokine signaling. This review explores the interplay between key epigenetic modifications and cancer immunity, emphasizing how these mechanisms contribute to immune escape and therapeutic resistance. We also examine the emergence of epigenetic therapies-particularly DNMT inhibitors, HDAC inhibitors, and BET inhibitors-as promising tools to reprogram immune responses and restore anti-tumor immunity. Furthermore, we discuss combinatorial approaches integrating epigenetic modulators with immune checkpoint inhibitors, underscoring their potential to enhance treatment efficacy. By outlining current challenges and emerging strategies, this review underscores the need for personalized epigenetic interventions and biomarker-driven approaches to improve outcomes in cancer immunotherapy. These insights establish epigenetic regulation as a critical frontier in next-generation cancer immunotherapy.
Therapeutic potential of extracellular vesicles in systemic lupus erythematosus: a systematic review.
Voltareli RV, Moretti NR, Puci GG … +1 more , Mori GG
Immunol Res · 2025 Aug · PMID 40815324 · Publisher ↗
Current therapies for Systemic lupus erythematosus (SLE), such as immunosuppressants and glucocorticoids, are associated with significant side effects, necessitating alternative treatment approaches. Extracellular vesicl...
Current therapies for Systemic lupus erythematosus (SLE), such as immunosuppressants and glucocorticoids, are associated with significant side effects, necessitating alternative treatment approaches. Extracellular vesicles (EVs) have emerged as a potential therapeutic option due to their immunomodulatory properties and ability to regulate innate and adaptive immune responses. Thus, the objective of the present study was to systematically analyze the therapeutic potential of EVs for treating SLE. A systematic review was conducted according to PRISMA guidelines. An electronic search was performed in the PubMed/ MEDLINE, Scopus, Cochrane Library and Open Gray databases covering the period up to September 2024 to respond to the PICO answer "Would EVs have therapeutic potential in SLE?" Control of Systemic lupus erythematosus progression and the cellular and molecular mechanisms present were considered the primary and secondary outcome, respectively. The bias risk of studies was evaluated by SYRCLE's RoB. A total of 7 studies met the inclusion criteria, and the data exhibited that EVs reduced disease severity, improved survival rates and ameliorated organ-specific damage in SLE models. It was seen that EVs reduction of autoantibody, Th17 and Tfh cells, type-1 macrophage, neutrophils and pro-inflammatory cytokines, alongside an increase in Tregs, immunosuppressive cytokines and type-2 macrophage. The studies showed high scientific evidence. EV therapy exhibits potential in mitigating SLE progression by modulating immune responses and reducing inflammation. Further research is required to confirm these datas in humans, facilitating advancement for future clinical applications.
GFAP as a marker of astrocytic damage correlated with medication overuse in migraine.
Carta S, Chiodega V, Tiberi R … +6 more , Pasquali A, Ferrari S, Bozzetti S, Ranieri F, Marchioretto F, Mariotto S
Immunol Res · 2025 Aug · PMID 40781571 · Full text
Different mechanisms are involved in migraine pathogenesis, including neurogenic inflammation, neurodegenerative processes, and a potential role of microglia. The aim of this study was to assess axonal and glial damage m...
Different mechanisms are involved in migraine pathogenesis, including neurogenic inflammation, neurodegenerative processes, and a potential role of microglia. The aim of this study was to assess axonal and glial damage measuring serum levels of neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) in migraine patients. Serum samples of 25 patients with episodic migraine (EM), 25 with chronic migraine (CM) diagnosed in accordance with the International Classification of Headache Disorders, 3rd edition (ICHD-3), and 50 age-matched healthy controls were prospectively collected. NfL and GFAP levels were assessed using ultrasensitive paramagnetic bead-based ELISA (SIMOA). Non-parametric tests were used for group comparison and 2-tailed Spearman analysis to assess correlations. GFAP levels were significantly increased in migraine patients (median 103.15 pg/mL [IQR 70.98-146.34] vs. 69.43 pg/mL [IQR 53.04-91.85], p < 0.001), particularly in those with medication overuse (106.08 [IQR 87.94-159.07] vs. 71.38 [IQR 54.16-135.06], p = 0.007), without difference between EM and CM (p = 0.985). Although NfL levels were not increased (p = 0.387), they were higher in patients with a long migraine course (rho 0.519, p < 0.001). Attack at sampling/days from last attack, migraine frequency/attack severity did not influence NfL or GFAP levels. Our findings demonstrate the occurrence of glial damage, particularly correlated with medication overuse, and the presence of axonal damage in the later disease stage, providing potential novel cues for the migraine pathogenesis.
The role of CD40L-expressing CXCR5CD8 follicular cytotoxic T cells in chronic lymphocytic leukemia.
Akboga F, Hindilerden F, Hindilerden IY … +3 more , Gulturk E, Deniz G, Gelmez MY
Immunol Res · 2025 Aug · PMID 40768060 · Publisher ↗
A newly identified cell subset within CD8T cells expressing CXCR5 of follicular cytotoxic T cells (T) lyse the infected or tumor cells. Recent studies have suggested that some T cell subsets may be involved in the regula...
A newly identified cell subset within CD8T cells expressing CXCR5 of follicular cytotoxic T cells (T) lyse the infected or tumor cells. Recent studies have suggested that some T cell subsets may be involved in the regulation of antibody responses. We aimed to determine the subset of T which differentiates in patients diagnosed with chronic lymphocytic leukemia (CLL) and their role in CLL immunopathogenesis. The peripheral blood mononuclear cells were isolated from 29 CLL patients and 19 healthy subjects. Intracellular IL-4, IL-17, IL-21, IFN-γ, perforin, and granzyme-B levels were investigated in T subsets. Increased levels of IL-4, IL-17, IL-21, IFN-γ and perforin, and decreased granzyme B expression levels were observed in CD40LT cells compared to the levels in CD40LT cells in the analysis of healthy individuals. T and its subsets were analyzed in CLL patients and healthy individuals, T and CD40LT cells were increased in CLL patients and there was a positive correlation between T and CD5CD19 cells. Moreover, increased number of T cells were detected in CLL patients with more progressive disease. Higher expression level of IL-4, IL-17, IL-21, and IFN-γ was observed in CD40LT cells of patients compared to the levels in healthy controls. Our findings might indicate that CD40LT cells may have a B cell activating role rather than exhibiting a cytotoxic role. Considering the effects of CD40LT cells on B cells, determining subsets of T cells which differentiate and understanding the functions of these subsets is crucial to elucidate their roles in the pathogenesis of B cell malignancies.
Immunoglobulin G4-related sclerosing mastitis: MRI findings and the literature review.
Wang L, Yang F, Hu X … +4 more , Li N, Gou J, Lin W, Zhang S
Immunol Res · 2025 Aug · PMID 40762735 · Publisher ↗
Immunoglobulin G4-related disease (IgG4-RD) is a rare immune-mediated fibro-inflammatory condition that can affect nearly any organ, with breast involvement (IgG4-related sclerosing mastitis, IgG4-RM) being exceptionally...
Immunoglobulin G4-related disease (IgG4-RD) is a rare immune-mediated fibro-inflammatory condition that can affect nearly any organ, with breast involvement (IgG4-related sclerosing mastitis, IgG4-RM) being exceptionally uncommon. This disease primarily affects middle-aged to elderly women and is frequently misdiagnosed as malignancy due to non-specific clinical and imaging features. We report a case of a 44-year-old woman with a painless right breast mass showing hypoechoic ultrasound findings and magnetic resonance imaging (MRI) characteristics, including a high ADC value and homogeneous enhancement with a persistent time-intensity curve (TIC). Histopathology confirmed IgG4-RM, with no recurrence after 12 months. A review of 24 published lectures highlights the diagnostic challenges and imaging variability of IgG4-RM.
Effects of belimumab on peripheral blood Breg cells and cytokines in childhood systemic lupus erythematosus.
Peng Q, Zhang R, Qiu S … +5 more , Yuan T, Lv J, Chen N, Lu Q, Zhong Z
Immunol Res · 2025 Aug · PMID 40762733 · Full text
To evaluate the therapeutic effectiveness of belimumab (BLM) in childhood systemic lupus erythematosus (cSLE) by analyzing peripheral blood Breg cell subsets and related cytokines at multiple time points post-treatment,...
To evaluate the therapeutic effectiveness of belimumab (BLM) in childhood systemic lupus erythematosus (cSLE) by analyzing peripheral blood Breg cell subsets and related cytokines at multiple time points post-treatment, compared with conventional therapy. From January 2023 to August 2023, 36 cSLE patients receiving BLM plus standard therapy (BLM group) and 35 receiving standard therapy alone (conventional group) were enrolled. Thirty age- and sex-matched healthy children were included as controls. Flow cytometry was used to detect absolute counts and ratios of peripheral Breg cell subsets at baseline, 6 weeks, 6 months, and 1 year. Serum cytokine levels (IL-2, IL-10, IL-21, IL-35, and IFN-γ) were measured by ELISA. After 6 weeks, IL-2, IL-21, and IFN-γ levels decreased significantly in both groups (P > 0.05 between groups); however, after 6 months and 1 year, these cytokines remained lower in the BLM group (all P < 0.05). IL-10 and IL-35 levels increased in both groups from week 6, with a milder increase in the BLM group (all P < 0.05). CD3⁻CD19⁺ B cells declined in both groups, with significant intergroup differences (P < 0.001). The BLM group showed a higher proportion of CD27⁺CD24⁺ B cells at week 6 compared to the conventional group (P < 0.05), but this reversed at 1 year (P < 0.05). CD38⁺CD24⁺ B cells were significantly higher in the BLM group at 6 months and 1 year (P < 0.001), while the conventional group showed no significant change after 6 weeks (P > 0.05). At baseline, the relative proportion of CD38⁺CD19⁺ B cells was higher in the BLM group than in the conventional treatment group (all P < 0.05). With ongoing treatment, both groups showed a decreasing trend in B cell proportions, with statistically significant differences observed within each group (all P < 0.05). Moreover, the decline in the BLM group was more pronounced compared to the conventional group at corresponding time points (all P < 0.05). Belimumab may exert immunomodulatory effects in childhood systemic lupus erythematosus by influencing peripheral Breg cell subsets and cytokine profiles. Compared with conventional therapy, it appears to provide more sustained regulation of certain immune parameters over time. These findings suggest its potential as a complementary therapeutic option targeting B cell dysregulation in cSLE, although further studies are needed to confirm these observations and clarify the underlying mechanisms.
SOCS1 improves abnormal IgA galactosylation in IgA nephropathy by regulating the TLR9/MyD88 pathway.
Huang Y, Wang Q, Lin C … +3 more , Qiu B, Chen S, Wang J
Immunol Res · 2025 Aug · PMID 40759858 · Publisher ↗
Abnormal galactosylation of IgA is a core factor in the development of IgA nephropathy (IgAN). Suppressor of cytokine signaling 1 (SOCS1) expression negatively correlates with IgA1 secretion in IgAN patients and that TLR...
Abnormal galactosylation of IgA is a core factor in the development of IgA nephropathy (IgAN). Suppressor of cytokine signaling 1 (SOCS1) expression negatively correlates with IgA1 secretion in IgAN patients and that TLR9/MyD88 promotes aberrantly glycosylated IgA formation. Therefore, the present study exposed whether SOCS1 is involved in aberrant galactosylation of IgA in IgAN by regulating the TLR9/MyD88 signaling pathway through in vivo and in vitro experiments. Differential expression of SOSC1 in IgAN patients and non-IgAN patients was analyzed using bioinformatics analysis and immunofluorescence. The IgAN mouse model and the IgA1-secreting DAKIKI cell model were used to validate the effect of SOCS1 on aberrant IgA galactosylation in IgAN. In addition, qRT-PCR, western blot, and immunohistochemistry experiments were performed to reveal the regulation of the TLR9/MyD88 pathway by SOCS1 in IgAN. The expression of SOCS1 was suppressed in renal tissues and peripheral blood mononuclear cells (PBMC) of IgAN patients, consistent with the results of dataset GSE35487. The expression of C1GALT1 in PBMC from IgAN patients was decreased and positively correlated with SOCS1 expression, while the expressions of TLR9 and MyD88 were increased and negatively correlated with SOCS1 expression. In vitro, SOCS1 overexpression inhibited the secretion of IgA1 and galactose-deficient IgA1 (Gd-IgA1) in DAKIKI cells, as well as the expression of TLR9. Knockdown of SOCS1 had the opposite effect. As a negative regulator of TLR9, SOCS1 inhibited the expression of TLR9, thereby preventing aberrant IgA galactosylation. MyD88 knockdown restored the CpG-ODN (TLR9 ligand)-induced overproduction of IgA1 and Gd-IgA1, and the reduction of C1GALT1. In vivo experiments demonstrated that SOCS1 significantly inhibited the production of aberrant glycosylated IgA IgG-IgA immune complexes and IL-6 in mice, reduced glomerular IgA, IgG, and C3 deposition and tethered cell proliferation, and alleviated renal injury. Decreased expression of SOCS1 contributes to IgAN pathogenesis by promoting aberrant IgA galactosylation via activating TLR9/MyD88 pathway. Our study may provide a prospective treatment target for IgAN.
Exploring the role of the Th9/IL-9 axis in atopic dermatitis: analysis of Th9 cells, PU.1 expression and serum IL-9 levels.
Shafi T, Rasool R, Bhat R … +4 more , Ayub S, Gull A, Rashid I, Koul AM
Immunol Res · 2025 Jul · PMID 40742612 · Publisher ↗
Atopic dermatitis (AD) is a chronic inflammatory skin disease resulting from complex interactions between genetic, environmental, and immunological factors, particularly the dysregulation of T helper (Th) cell subsets. W...
Atopic dermatitis (AD) is a chronic inflammatory skin disease resulting from complex interactions between genetic, environmental, and immunological factors, particularly the dysregulation of T helper (Th) cell subsets. While Th2 responses have been central to AD research, evidence highlights the role of Th9 cells and their signature cytokine, interleukin-9 (IL-9), in allergic inflammation. However, the involvement of the Th9/IL-9 axis in AD remains insufficiently characterized. This study investigates the role of the Th9/IL-9 axis in AD through an integrated clinical, immunological, and molecular approach. The study comprised a total of 89 subjects, consisting of 54 AD cases and 35 healthy controls. Disease severity and allergen sensitivity were assessed using SCORAD scores and skin prick testing, respectively. PU-1 mRNA was quantified using real-time PCR. Th9 cell frequency was determined through flow cytometry, vitamin D levels were measured by chemiluminescence, and total IgE and IL-9 levels were estimated using ELISA. AD patients demonstrated a significant increase in circulating Th9 cell frequency (11.5 ± 0.3% vs. 5.0 ± 0.5%, p < 0.0001), PU.1 mRNA expression with an average 2.5-fold upregulation (p < 0.001), and elevated serum IL-9 concentrations (18.6 ± 6.3 pg/mL vs. 8.3 ± 1.9 pg/mL, p < 0.0001) compared to healthy controls. Stratified analysis revealed significant associations of PU.1 mRNA and IL-9 levels with rural residence, vitamin D deficiency, and peripheral eosinophilia (p < 0.05). Allergen sensitivity, as determined by skin prick testing, was positive in 50% of AD patients, and 66.7% exhibited elevated total serum IgE levels. Our findings underscore the involvement of the Th9/PU.1/IL-9 axis in the immunopathogenesis of AD. The observed upregulation of Th9 cell frequency, PU.1 expression, and IL-9 levels suggests a contributory role of Th9-mediated pathways in disease development and severity. These results provide a foundation for future studies investigating the dynamic crosstalk between Th9 cells, other immune cell subsets, and epidermal components, with the aim of identifying novel immunomodulatory targets for precision therapy in AD.
Severe interstitial lung disease as the first manifestation of a STING1 variant in a familial case.
Kang Z, Fu R, Li Z … +1 more , Zhang L
Immunol Res · 2025 Jul · PMID 40731159 · Publisher ↗
STING-associated vasculopathy with onset in infancy (SAVI) is a very rare autosomal-dominant Mendelian autoinflammatory disease caused by heterozygous gain-of-function mutations in STING1. Reported carriers of a STING1 g...
STING-associated vasculopathy with onset in infancy (SAVI) is a very rare autosomal-dominant Mendelian autoinflammatory disease caused by heterozygous gain-of-function mutations in STING1. Reported carriers of a STING1 gain-of-function mutations are mostly symptomatic. Herein, we present a case study of an infant who presented with cyanosis, dyspnea, clubbing fingers, failure to thrive, and widespread interstitial changes, all consistent with interstitial lung disease (ILD); however, there was a notable lack of characteristic cutaneous features and recurrent fever. Whole-exome sequencing detected a pathogenic heterozygous mutation (p.Arg218Gln) in STING1. Intriguingly, this mutation was also present in her father (aged 32 years), whereas this carrier was healthy and without clinical symptoms. This study emphasizes the need to consider the possibility of SAVI in infants with ILD, even if they lack typical manifestations. Our study also underlines the possibility that carriers with STING gain-of-function mutations are clinically asymptomatic.
SPP1 + macrophages facilitate pancreatic cancer progression via ITGB6-mediated interactions: evidence from integrated multi-omics analysis and experimental validation.
Ge J, Cai J, Zhang G … +2 more , Li D, Tao L
Immunol Res · 2025 Jul · PMID 40719841 · Publisher ↗
Basement membranes (BMs) and tumor-associated macrophages (TAMs) are crucial stromal components in pancreatic cancer (PC), critically influencing disease progression. Bulk and single-cell RNA-seq (scRNA-seq) data were ac...
Basement membranes (BMs) and tumor-associated macrophages (TAMs) are crucial stromal components in pancreatic cancer (PC), critically influencing disease progression. Bulk and single-cell RNA-seq (scRNA-seq) data were acquired from publicly available databases. Through integration of multiple machine learning algorithms, we developed and validated a BM-related subtype and prognostic signature in PC cohorts. The expression profiles of BM-related genes in PC were verified using experimental approaches. We further investigated the functional mechanisms of a core gene in PC progression. Additionally, we characterized the TAM landscape in PC, revealing distinct TAM subsets associated with tumor progression and their dynamic interactions with BM components. Based on BM-related gene expression profiles, PC samples were stratified into two distinct subtypes. Our integrated prognostic signature combining LASSO and survival-SVM algorithms demonstrated robust performance in predicting PC outcomes and clinical characteristics. LAMA3, ITGA3, and ITGB6 showed higher expression in PC specimens versus normal controls. Functional experiments confirmed that ITGB6 knockdown markedly suppressed PC progression. Through integrative analysis of multiple scRNA-seq datasets of PC, we established a single-cell landscape of TAMs and ductal cells, respectively. SPP1 + TAMs correlated with poor PC prognosis and facilitated tumor progression through ITGB6-mediated interactions. In this study, we established novel PC subtypes and constructed a prognostic signature based on BM-related genes. An atlas of TAMs was constructed in PC. SPP1 + macrophages drove pancreatic cancer progression via ITGB6-mediated interactions.
Molecular mechanisms and treatment strategies for discogenic lumbar pain.
Yan S, Han B, Song C … +1 more , Yan L
Immunol Res · 2025 Jul · PMID 40715592 · Publisher ↗
Discogenic low back pain (DLBP) is one of the main causes of chronic low back pain, and its core pathological mechanism is due to various molecular changes caused by intervertebral disc degeneration. The normal intervert...
Discogenic low back pain (DLBP) is one of the main causes of chronic low back pain, and its core pathological mechanism is due to various molecular changes caused by intervertebral disc degeneration. The normal intervertebral disc is composed of the nucleus pulposus, annulus fibrosus, and cartilaginous endplate, and has structural characteristics without blood vessels or nerves, relying on dispersed support to maintain homeostasis. During the process of degeneration, nucleus pulposus cells undergo apoptosis and cell senescence, its synthesis ability decreases, and the balance of extracellular matrix (ECM) is disrupted. Meanwhile, inflammatory factors such as IL-1β and TNF-α are continuously upregulated, activating pathways such as NF-κB and MAPK, inducing the expression of MMPs and ADAMTS, and accelerating ECM degradation. Matrix disruption further promotes the release of neurotrophic factors (such as NGF, VEGF), induces angiogenesis and nerve fiber invasion into the nucleus pulposus area, destroys the immune barrier, and leads to peripheral nerve sensitization. The central system mediates central remodeling through factors such as BDNF and CGRP, maintaining and amplifying pain signals. This article systematically summarizes the molecular mechanism of DLBP and summarizes relevant treatment strategies based on it, including conservative treatments such as NSAIDs, interventional methods such as radiofrequency ablation and fusion, as well as emerging therapies such as targeted anti-inflammatory, anti-neurogenic, matrix protection, and stem cell regeneration. The aim is to provide theoretical support and research directions for personalized treatment and mechanism interventions of DLBP.
PS77: a novel peptide with α-helical structure for targeted anti-inflammatory therapy in biomaterials design.
Lin Z, Zhao H, Lin H … +3 more , Song L, Tian X, Choo SW
Immunol Res · 2025 Jul · PMID 40705171 · Full text
Chronic inflammation underlies many diseases, posing challenges in therapeutic management due to the limitations and side effects of current treatments and necessitating novel therapeutic solutions. Here, we introduce PS...
Chronic inflammation underlies many diseases, posing challenges in therapeutic management due to the limitations and side effects of current treatments and necessitating novel therapeutic solutions. Here, we introduce PS77, a novel α-helical peptide derived from Squama Manitis, a Traditional Chinese Medicine, and unveil its remarkable anti-inflammatory properties, potentially revolutionizing biomaterials design for targeted anti-inflammatory therapies. An in vitro TNF-α-induced inflammatory model in human keratinocytes (HaCaT cells) was used to demonstrate PS77's significant impact. We demonstrated that PS77 significantly reduced IL-8 and MMP-3 expression, indicating potent anti-inflammatory activity without cytotoxicity to normal cells. Transcriptomic analysis further elucidated PS77's mechanism of action, revealing significant modulation of 265 genes (137 upregulated and 128 downregulated), with a particular focus on the downregulation of genes within the BMP and TGF-β signaling pathways-key players in inflammation. Moreover, PS77 regulated several inflammation-associated genes, including CHRNA7, CXCR5, RXRG, KRT76, IL12RB2, and COLEC11, underscoring its comprehensive anti-inflammatory effects. This study not only highlights PS77's therapeutic potential as a biomaterial for treating inflammatory diseases but also paves the way for further research into its mechanisms and applications in biomedicine. By leveraging the novel biomaterial properties of PS77, this research may contribute to the development of targeted and efficient anti-inflammatory therapies, marking a significant advance in the field of biomaterials and offering a promising avenue for inflammation management.
Spon2 knockdown suppresses the phenotype of house dust mite-induced allergic asthma in mice and cells.
Zheng H, Ding S, Rong D … +2 more , Li T, Xiong M
Immunol Res · 2025 Jul · PMID 40691739 · Publisher ↗
Allergic asthma is a chronic inflammatory disease of the airways. The objective of this study was to identify potential therapeutic targets for allergic asthma through RNA sequencing (RNA-seq) and experimental analyses....
Allergic asthma is a chronic inflammatory disease of the airways. The objective of this study was to identify potential therapeutic targets for allergic asthma through RNA sequencing (RNA-seq) and experimental analyses. Allergic asthma models, both in cells and mice, were induced using house dust mite (HDM) treatment. RNA-seq analysis of lung tissues from HDM-induced allergic asthma mice and control mice was performed to identify differentially expressed genes (DEGs), and functional enrichment analysis of DEGs was performed. Spon2 knockdown was achieved via siRNA transfection and adeno-associated virus transduction. Bronchoalveolar lavage fluid (BALF) from mice was analyzed using cytology, ELISA for cytokines, and Giemsa staining. Lung tissues underwent HE staining, immunohistochemical staining, and Masson staining. Key gene expression levels were monitored in cellular and mouse models using real-time quantitative PCR and western blotting. RNA-seq and histological analysis of the HDM-induced allergic asthma mouse model revealed increased macrophage infiltration and upregulation of Spon2 in the lung tissues of mice with allergic asthma. Compared with the HDM-induced group, Spon2 knockdown led to decreased levels of inflammatory cytokines in the cellular model and, in the mouse model, it relieved HDM-caused histopathological alterations in mouse lungs, reduced collagen fiber deposition, lowered HDM-specific IgE expression in serum, and mitigated the HDM-induced increase in CD80 expression in lung tissues, total cell counts, and cytokine levels (IL-13, TNF-α, IFN-γ, IL-4, IL-5, IL-10) in BALF. Spon2 plays a role in the progression of HDM-induced allergic asthma and may be a potential therapeutic target worthy of further in vivo investigation.
The role of dendritic cells in recurrent pregnancy loss.
Yuan X, Li C, Yang L … +2 more , Zhang X, Feng X
Immunol Res · 2025 Jul · PMID 40690072 · Publisher ↗
Recurrent pregnancy loss (RPL), defined as ≥ 2 consecutive losses, remains a significant clinical challenge with complex immunological underpinnings. While immune dysfunction underpins RPL, dendritic cells (DCs) emerge a...
Recurrent pregnancy loss (RPL), defined as ≥ 2 consecutive losses, remains a significant clinical challenge with complex immunological underpinnings. While immune dysfunction underpins RPL, dendritic cells (DCs) emerge as central regulators of maternal-fetal tolerance. This review comprehensively explores the multifaceted roles of DC subsets at the maternal-fetal interface, including their contribution to immune tolerance, angiogenesis, placental development, and bidirectional interactions with trophoblasts and natural killer (NK) cells. We detail specific DC alterations in RPL, encompassing phenotypic shifts, functional defects, and disrupted DC-NK cell crosstalk, linking these changes to pregnancy loss risk. Emerging evidence highlights therapeutic strategies targeting DCs, such as tolerogenic DC vaccines and interventions modulating trophoblast MHC antigen presentation, alongside established immunomodulation, to restore immune balance. Underlying mechanisms like systemic inflammation impacting endometrial DCs are also discussed. By synthesizing current literature and controversies, this review elucidates the critical, yet complex, role of DC heterogeneity and function in RPL pathogenesis and discusses innovative interventions aimed at improving pregnancy outcomes.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe