Immunologic Research[JOURNAL]
Sun
200 papers
GLP-1 and its derivatives are associated with the reduction of macrophage infiltration and inflammation in systemic chronic inflammatory diseases: a systematic review and meta-analysis of animal models.
Sha H, Shi Y, Li Y … +2 more , Yang H, Huo R
Immunol Res · 2026 Mar · PMID 41843040 · Publisher ↗
Long-term infiltration of macrophages will aggravate chronic low-grade inflammation in the body. Here, we aim to evaluate the changes in F4/80 (total macrophage markers), M1/M2 macrophage markers and inflammatory cytokin...
Long-term infiltration of macrophages will aggravate chronic low-grade inflammation in the body. Here, we aim to evaluate the changes in F4/80 (total macrophage markers), M1/M2 macrophage markers and inflammatory cytokines following intervention with GLP-1 and its derivatives in animal models. We conducted an electronic literature search on 7 databases from establishment to November 1, 2024. The primary outcomes were the mRNA and protein expression of F4/80. The secondary outcomes were changes in M1/M2 macrophage markers and inflammatory factor. A total of 368 studies were screened according to pre-determined inclusion and exclusion criteria. Finally, 25 studies were included in this meta-analysis. Overall, GLP-1 and its derivatives reduced F4/80 mRNA (P < 0.0001) and F4/80 protein levels (P < 0.0001) in experimental groups. For M1 macrophage markers, compared with the control group, the levels of Tlr-4 mRNA (P < 0.0001) and iNOS mRNA (P = 0.001) related to inflammation were decreased in experimental groups. However, compared with the control group, the changes of M2 macrophage markers in the experimental group were not statistically significant, such as CD163 mRNA levels (P = 0.09), CD206 mRNA levels (P = 0.44) and Arg-1 mRNA levels (P = 0.34). Compared with the control group, the levels of relevant pro-inflammatory factors, such as IL-6 mRNA (P < 0.0001), TNF-α mRNA (P < 0.0001) and IL1-β mRNA (P < 0.0001), were decreased in experimental groups. The mRNA level of anti-inflammatory factor IL-10 in experimental group was higher than that in control group (P = 0.0003). Compared with the control group, the levels of MCP-1 mRNA (P < 0.0001) related to inflammation were decreased in experimental groups. In addition, the results of our analysis indicated a reduction in CCR2 mRNA levels in animals subjected to the intervention compared to the control group (P < 0.0001). Our study suggests that GLP-1 and its derivatives are associated with the reduction of macrophage infiltration and inflammation in systemic chronic inflammatory diseases.
The Fas-FasL system: from apoptosis regulator to therapeutic target in autoimmunity, cancer, and transplantation.
Gadelkarim M, Elsayed A, Nazir A … +4 more , Elsayed Y, Habashneh A, Iqbal O, Rawashdeh B
Immunol Res · 2026 Mar · PMID 41838231 · Publisher ↗
The Fas-FasL system is a central regulator of apoptosis, immune homeostasis, and tissue equilibrium. This pathway is mediated by Fas (CD95/APO-1) and its ligand FasL (CD95L/APO-1 L), which upon interaction assemble the d...
The Fas-FasL system is a central regulator of apoptosis, immune homeostasis, and tissue equilibrium. This pathway is mediated by Fas (CD95/APO-1) and its ligand FasL (CD95L/APO-1 L), which upon interaction assemble the death-inducing signaling complex (DISC) and initiate downstream signaling cascades that can result in apoptosis or non-apoptotic immune responses. Dysregulation of this pathway contributes to diverse pathologies. Impaired expression or signaling of Fas or FasL disrupts the elimination of autoreactive lymphocytes, undermining self-tolerance and promoting autoimmune disease. Fas-FasL interactions also play a critical role in balancing effector and regulatory T-cell responses. These insights have driven interest in combination therapies that modulate Fas signaling alongside immunosuppressive agents to enhance efficacy while minimizing toxicity. Future therapeutic strategies will require selective targeting of disease-specific Fas/FasL-expressing cells to avoid damage to healthy tissues. Advances in targeted delivery platforms, including nanoparticles and antibody-based carriers, may improve this specificity. Continued investigation into how Fas-FasL integrates with other immune checkpoints, such as PD-1/PD-L1 and CTLA-4, will be essential for designing synergistic immunomodulatory approaches. Collectively, this review highlights the multifaceted roles of the Fas-FasL pathway and its emerging therapeutic potential in cancer, autoimmune disorders, and allograft tolerance.
Adapting covid-19 vaccination through targeted approaches: FDA-approved vaccines for the 2025-2026 season.
Begum RF, Mathew M, Doshi PP … +1 more , Suresh S
Immunol Res · 2026 Mar · PMID 41831154 · Publisher ↗
Since the identification of SARS-CoV-2 in late 2019, the continuous evolution of viral variants has represented a challenge to vaccination efforts worldwide. The recent emergence of Omicron viral sublineages has urged th...
Since the identification of SARS-CoV-2 in late 2019, the continuous evolution of viral variants has represented a challenge to vaccination efforts worldwide. The recent emergence of Omicron viral sublineages has urged the need for updated vaccine formulations in order to maintain efficacy, especially among high-risk populations who are susceptible to severe COVID-19 manifestations. This review aims to comprehend how COVID-19 vaccination strategies evolved and to accentuate FDA-approved vaccines for the 2025–2026 season. The 2025–2026 FDA-approved vaccines- Pfizer-BioNTech’s Comirnaty® LP.8.1, Moderna’s Spikevax LP.8.1 (and mNEXSPIKE), and Novavax’s Nuvaxovid LP.8.1-target the JN.1 variant and elicit strong neutralising antibody responses. Real-world results suggest a relatively low risk of hospitalisation and mortality connected to COVID-19 among persons aged 65 years and older. Safety profiles were consistent with previous formulations, and no new safety concerns were noted. Economic models further add to the cost-effectiveness of vaccination in lowering hospitalisations and healthcare burden in high-risk groups. COVID-19 Vaccinations updated for the 2025–2026 season are highly immunogenic and well protective against severe COVID manifestations in a high-risk cohort. Targeted vaccination strategies, tuned to the variants’ changing dynamics, are required to diminish COVID-19’s global impact while ensuring equity in protection for the most vulnerable population segments.
Knockdown of LncRNA NIFK-AS1 inhibits the activation of CD4 + T cells in systemic lupus erythematosus by regulating the let-7f-5p/STAT3 axis.
Zhou Y, Huang L, Yang H … +4 more , Wang S, Wang F, Li L, Huang G
Immunol Res · 2026 Mar · PMID 41831116 · Publisher ↗
SLE is marked by dysregulated T cell activation, which consequently triggers the excessive generation of autoantibodies. Long non-coding RNAs (lncRNAs) may be associated with autoimmune and inflammatory diseases, and NIF...
SLE is marked by dysregulated T cell activation, which consequently triggers the excessive generation of autoantibodies. Long non-coding RNAs (lncRNAs) may be associated with autoimmune and inflammatory diseases, and NIFK-AS1 has been found to be abnormally expressed in SLE. The aim of this study is to explore the abnormal expression and clinical role of NIFK-AS1 in SLE patients, and to investigate whether NIFK-AS1 regulates the expression of let-7f-5p to participate in the immune mechanism of SLE. This study included 88 healthy controls and 95 SLE patients and compared the expression levels of NIFK-AS1 in two groups. CD4 + T cells were extracted from the peripheral blood of patients in both groups, and the expression levels of NIFK-AS1 were overexpressed or knocked down through transfection technology. The impact of NIFK-AS1 on the activation of CD4 + T cells was also investigated. Furthermore, the relationship between the NIFK-AS1/let-7f-5p/STAT3 axis was verified through a dual-luciferase assay. Elevated levels of NIFK-AS1 were observed in both the serum and T cells of individuals with SLE. Furthermore, the expression of NIFK-AS1 is significantly correlated with the clinical indicators of SLE patients. NIFK-AS1 has a significant diagnostic effect on SLE. Functionally, the inhibition of NIFK-AS1 led to suppressed activation of healthy T cells and a reduction in the auto-reactivity of SLE-derived CD4 + T cells. Conversely, let-7f-5p inhibitor mitigated the inhibitory effects induced by NIFK-AS1 knockdown on CD4 + T cell activation. Furthermore, NIFK-AS1 promoted STAT3 expression by inhibiting let-7f-5p. The NIFK-AS1/let-7f-5p/STAT3 axis is significantly involved in T cell activation within SLE, thereby offering a promising therapeutic target for the management of this disease.
The investigation of immunomodulatory effects of didemnin B in macrophage cells.
Dağ HE, Atalay BR, Ayaz F … +2 more , Ayaz EA, Deviren A
Immunol Res · 2026 Mar · PMID 41820646 · Full text
Didemnins, which are cyclic depsipeptides originating from marine sources, have gained significant interest owing to their potent anti-cancer properties. Among them, Didemnin B exhibits potent anti-tumor effects; however...
Didemnins, which are cyclic depsipeptides originating from marine sources, have gained significant interest owing to their potent anti-cancer properties. Among them, Didemnin B exhibits potent anti-tumor effects; however, its poor bioavailability and dose-limiting toxicity have thus far restricted its clinical application. Understanding its immunological impact is therefore essential for optimizing its therapeutic potential and supporting ongoing efforts to develop Didemnin B as a clinically viable agent. This study aimed to investigate the immunomodulatory effects of Didemnin B on macrophage function, with a particular focus on its potential relevance to immunotherapeutic and chemotherapeutic applications. In this context, Didemnin B was applied at concentrations of 1, 5, and 10 µg/mL to RAW 264.7 macrophages, based on dose ranges previously reported in the literature. The production of TNF-α, IL-6, GM-CSF, and IL-12p40 was evaluated under both unstimulated and LPS-stimulated conditions. Cytokine levels in cell culture supernatants were measured using ELISA to assess how Didemnin B modulates macrophage cytokine responses. Our findings demonstrate that Didemnin B suppresses the production of TNF-α, IL-6, GM-CSF, and IL-12p40 in RAW 264.7 macrophages, indicating a robust inhibitory effect on pro-inflammatory cytokine secretion. Didemnin B significantly attenuates LPS-induced inflammatory responses in RAW 264.7 macrophages by suppressing key pro-inflammatory cytokines, indicating its potential as a potent anti-inflammatory and immunomodulatory agent.
Association between osteoporosis and cardiovascular disease in women and the mediating role of inflammatory biomarkers: based on the NHANES database : Mediating role of inflammatory biomarkers between OP and CVD in women.
Zhang B, Jiang Y, Zhou L … +3 more , Li X, Huang J, Xiao J
Immunol Res · 2026 Mar · PMID 41817853 · Publisher ↗
Monocyte-to-lymphocyte ratio (MLR) and systemic inflammation response index (SIRI) are independently associated with osteoporosis (OP) and cardiovascular disease (CVD). However, whether MLR and SIRI mediate the relations...
Monocyte-to-lymphocyte ratio (MLR) and systemic inflammation response index (SIRI) are independently associated with osteoporosis (OP) and cardiovascular disease (CVD). However, whether MLR and SIRI mediate the relationship between OP and CVD remains unknown. To investigate the linkage between OP and CVD prevalence in women and the mediating role of MLR and SIRI. Data were obtained from the NHANES. Logistic regression and restricted cubic spline analyses were used to explore the associations among OP, femoral bone mineral density (BMD), and CVD prevalence in women. Subgroup analyses were conducted to examine differences in the linkage between OP and CVD prevalence among different populations. Mediation analyses were performed to assess the mediating effects of MLR and SIRI in the aforementioned associations. Subgroup analysis evaluated association heterogeneity; mediation analysis assessed MLR and SIRI mediating effects. 2,292 participants were included. Logistic regression showed that in Model III, OP was positively linked with CVD prevalence in women (OR = 2.09, 95% CI: 1.02–4.28, P = 0.044). Furthermore, in Model III, total femur BMD (OR = 0.06, 95% CI: 0.01–0.53, P = 0.013) and intertrochanteric BMD (OR = 0.06, 95% CI: 0.01–0.39, P = 0.004) were negatively associated with CVD prevalence in women, with no evidence of non-linear associations (P-non-linear > 0.05). Subgroup analysis revealed a stronger association in non-estrogen-users, women with a high school education or lower, and physically inactive women. MLR and SIRI mediated 6.27% and 5.66% of the association between OP and CVD prevalence, respectively. OP and CVD prevalence are significantly positively correlated in the female population, which is partially mediated by the systemic inflammatory markers MLR and SIRI. These findings provide new insights for cardiovascular risk management in women with OP in clinical practice.
Memory-biased CD8αα⁺ T cells show reduced abundance and phenotypic remodeling in SLE.
Xiong Z, Xue T, Zhou S … +6 more , Liang Y, He J, Wei Y, Gao Y, Sun X, Liu C
Immunol Res · 2026 Mar · PMID 41801506 · Publisher ↗
To characterize peripheral CD8αα⁺ T cells in systemic lupus erythematosus (SLE), evaluate their quantitative and phenotypic alterations, and examine associations with autoantibody profiles and inflammatory markers. Forty...
To characterize peripheral CD8αα⁺ T cells in systemic lupus erythematosus (SLE), evaluate their quantitative and phenotypic alterations, and examine associations with autoantibody profiles and inflammatory markers. Forty treatment-naïve SLE patients and 46 age- and sex-matched healthy controls were recruited. Peripheral blood mononuclear cells were analyzed by flow cytometry to quantify CD8αα⁺ and CD8αβ⁺ T-cell subsets, differentiation states (TN, TCM, TEM, TEMRA), and expression of CCR7, CD45RA, CD28, CD27, GZMB, perforin, and GPR56. Correlations with autoantibodies, immunoglobulin levels, complement, and inflammatory markers were assessed. In healthy controls, CD8αα⁺ T cells were less abundant than CD8αβ⁺ T cells and predominantly enriched in central memory (TCM) and terminally differentiated effector memory RA⁺ (TEMRA) subsets, with lower CD28, CD27, CCR7, and GZMB expression. In SLE patients, CD8αα⁺ T cells showed further reductions in absolute counts, decreased CD28, and increased GZMB and GPR56, while differentiation subset distribution remained unchanged. Alterations in CD8αα⁺ T-cell counts and marker expression correlated with autoantibody titers, immunoglobulin levels, complement C4, and inflammatory indices. Peripheral CD8αα⁺ T cells form a distinct memory-enriched subset that is numerically reduced and phenotypically remodeled in SLE. Their quantitative and phenotypic alterations correlate with immunological and inflammatory parameters.
TNFR-CD3-engineered regulatory T cells attenuate neuroinflammation and neuropathic pain.
Li P, Yan Y, Wu S … +2 more , He P, Wang W
Immunol Res · 2026 Mar · PMID 41787027 · Publisher ↗
Background: Neuropathic pain is a debilitating condition characterized by neuronal hyperexcitability and neuroimmune dysregulation. Regulatory T cells (Tregs) are critical for immune homeostasis, but their survival and f...
Background: Neuropathic pain is a debilitating condition characterized by neuronal hyperexcitability and neuroimmune dysregulation. Regulatory T cells (Tregs) are critical for immune homeostasis, but their survival and function are severely impaired in the inflammatory milieu, particularly under the influence of tumor necrosis factor-α (TNF-α). Objective This study aimed to determine whether engineering Tregs with a TNFR-CD3 fusion construct could enhance their stability, survival, and therapeutic efficacy in a rat model of chronic constriction injury (CCI). Methods: CD4⁺CD25⁺ Tregs were isolated from rats, transduced with a TNFR-CD3ζ-IRES-GFP lentiviral construct, and characterized for proliferation, apoptosis, and chemotaxis in vitro. CCI was induced by loose ligation of the sciatic nerve. Rats received adoptive transfer of either unmodified Tregs or TNFR-CD3 Tregs. Behavioral assays assessed mechanical hypersensitivity, while flow cytometry and molecular analyses evaluated immune cell infiltration, phenotype, and signaling pathway activation in the spinal cord. Results: Endogenous Tregs were insufficient to control CCI-induced inflammation: depletion exacerbated hypersensitivity, and adoptive transfer of unmodified Tregs failed to relieve pain due to apoptosis in the TNF-rich environment. In contrast, TNFR-CD3 Tregs retained TNF-induced chemotaxis, exhibited enhanced proliferation without increased apoptosis, and persisted in vivo. Adoptive transfer of TNFR-CD3 Tregs significantly improved paw withdrawal thresholds, reduced macrophage infiltration, and promoted an M2-like phenotype. Microglial activation and pro-inflammatory cytokine production were markedly suppressed, accompanied by decreased NF-κB/p65 and MAPK phosphorylation. Additionally, TNFR-CD3 Tregs limited neutrophil infiltration, reduced IL-1β, TNF, IL-6, and MMP secretion, and attenuated ROS and superoxide production. Conclusion: TNFR-CD3 Tregs effectively reprogram the neuroimmune microenvironment by modulating macrophages, microglia, and neutrophils, thereby alleviating neuropathic pain. These findings highlight engineered Treg therapy as a promising immunomodulatory strategy for neuroinflammatory diseases and support its potential translational application in neuropathic pain management.
Reduction of regulatory B cells is associated with high-risk clinical stratification in antiphospholipid syndrome patients.
Ma R, Wang YY, Feng JH … +2 more , Li WY, Long Y
Immunol Res · 2026 Mar · PMID 41784711 · Publisher ↗
Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by the presence of antiphospholipid antibodies (aPLs). B cells are known to play a crucial role in pathogenesis of APS, however, the contribution of...
Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by the presence of antiphospholipid antibodies (aPLs). B cells are known to play a crucial role in pathogenesis of APS, however, the contribution of regulatory B cells (Bregs) remains unexplored. Our study aimed to evaluate the changes of Bregs in APS patients, and further explored their potential clinical significance. We comparatively assessed and compared the changes of Bregs (defined as CD19+CD24highCD38high and CD19+CD27+CD24high) among 55 cases of APS patients (including 36 cases of pAPS patients and 19 cases of non-criteria APS patients), 44 systemic lupus erythematosus (SLE) patients, and 30 cases of healthy controls (HCs) using flow cytometry. The adjusted global antiphospholipid syndrome score (aGAPSS) was calculated for the risk stratification of APS patients. Additionally, associations of Bregs with serum aPLs status and aGAPSS were evaluated by correlation analysis or/and receiver operating characteristic (ROC) analysis. We found that APS patients exhibited significantly lower levels of CD19+CD24highCD38highBregs and CD27+CD24highBregs compared with HCs, and were significantly decreased in patients of high-risk (aGAPSS ≥ 10) compared to low-risk patients. In addition, both CD19+CD24highCD38highBregs and CD27+CD24highBregs were inversely correlated with aGAPSS. ROC curve showed that the combination of CD24highCD38highBregs and CD27+CD24highBregs improved the discriminatory performance for identifying high-risk patients (AUC = 0.753), compared with each Bregs alone. Notably, the levels of Bregs were lowest in triple positive aPLs APS patients. In subgroup analyses, a higher frequency of CD24highCD38highBregs was observed in patients with a history of thrombosis. Our results suggested that Bregs may be associated with high-risk aPL profiles and aGAPSS-based risk stratification in APS.
CRISPR-Cas9-based gene editing as a proof-of-concept approach in an inborn error of immunity caused by a DCLRE1C variant.
Duran T, Karaselek MA, Dagdelen B … +4 more , Kuccukturk S, Guner SN, Keles S, Reisli I
Immunol Res · 2026 Feb · PMID 41762386 · Full text
Hypomorphic DCLRE1C variants impair T and B cell development, leading to combined immunodeficiency (CID) or leaky severe combined immunodeficiency (SCID). Current treatment options, such as allogeneic hematopoietic stem...
Hypomorphic DCLRE1C variants impair T and B cell development, leading to combined immunodeficiency (CID) or leaky severe combined immunodeficiency (SCID). Current treatment options, such as allogeneic hematopoietic stem cell transplantation (aHSCT), are associated with significant risks, highlighting the need for alternative therapeutic strategies. In this study, we report the first a proof-of-concept CRISPR-Cas9–mediated correction of a hypomorphic DCLRE1C variant (c.194 C > T; p.T65I) in CD4 + helper T (Th) cells using CRISPR-Cas9 gene-editing technology. CD4 + Th cells were isolated, and the variant region was edited with sgRNA and donor DNA. Gene editing efficiency was confirmed by Sanger sequencing, revealing successful restoration of the target region to its wild-type sequence. Functional analyses showed a significant increase in CD25 activation and Artemis protein expression post-editing, although DCLRE1C mRNA levels remained unchanged. The approximately 6–8% increase in CD25 expression was statistically significant but did not reach healthy control levels. These findings suggest that CRISPR-Cas9 –mediated gene editing may enable precise correction and induce measurable cellular-level functional changes, supporting biological feasibility rather than therapeutic efficacy. This study provides a foundation for future research on HSCs and underscores the potential role of CRISPR-Cas9–based approaches in the treatment of inborn errors of immunity (IEIs) associated with DCLRE1C variants.
Immunopsychiatry: current concepts and future directions.
Messina A
Immunol Res · 2026 Feb · PMID 41731225 · Publisher ↗
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Efficacy of chimeric antigen receptor natural killer cells in treatment of ovarian cancer. A meta-analysis of pre-clinical studies.
Ahmed N, Jabeen J, Rehman M … +8 more , Noor S, Tahseen S, Qamar A, Anas M, Khalid MM, Ahmad T, Wang W, Lyu L
Immunol Res · 2026 Feb · PMID 41714550 · Publisher ↗
Chimeric antigen receptor (CAR) therapies have expanded beyond T-cells with addition of natural killer (NK) cells. In ovarian cancer, long-term survival remains poor with the rising need for new therapies. Therefore, thi...
Chimeric antigen receptor (CAR) therapies have expanded beyond T-cells with addition of natural killer (NK) cells. In ovarian cancer, long-term survival remains poor with the rising need for new therapies. Therefore, this meta-analysis evaluated the pre-clinical efficacy of emerging CAR-NK therapies in ovarian cancer models. Following PRISMA-guidelines and registered protocol (PROSPERO, CRD420251131530), literature from PubMed, Web of Science, and Scopus was retrieved till 30-06-2025 for pre-clinical in-vivo studies of CAR-NK therapy in ovarian cancer. Studies without in-vivo components or human CAR-NK were excluded. Primary outcomes were ratio of means (ROM) for tumor burden and median survival ratio (MSR). Data was analyzed in JASP™ and risk of bias (RoB) was determined using SYRCLE's RoB tool for animal studies. Fourteen experiments (21 CAR-NK groups) were included. CAR-NK significantly reduced tumor burden versus untreated controls (ROM 0.09 [0.03-0.32], p < 0.001) and unmodified/mock NK-cells (ROM 0.18 [0.08-0.42], p < 0.001). Survival was significantly prolonged (MSR 1.67 [1.31-2.14] vs. control; 1.40 [1.08-1.83] vs. unmodified/mock NK, both p < 0.05). Subgroup analyses revealed no significant modifiers, though trends favored mesothelin-targeted and NK-92-based CARs. Limited safety data indicated no cytokine release syndrome or graft-versus-host disease. Small sample size in subgroup analyses and unclear RoB in certain areas are some limitations of this study. However, the pooled estimates were robust to sensitivity analyses and relatively insignificant heterogeneity in survival outcomes could be important for poor long-term survival in ovarian cancers. CAR-NK demonstrates potential pre-clinical efficacy in ovarian cancer models, outperforming naive NK-cells with a consistent survival benefit.
The role of metal metabolism in inflammatory bowel disease: Pathogenesis, clinical application, and therapeutic targets.
Zhao H, Sun Y, Li L … +4 more , Zhang Z, Xu X, Cui D, Wu Y
Immunol Res · 2026 Feb · PMID 41714459 · Publisher ↗
Inflammatory bowel disease (IBD) refers to a group of chronic and recurrent inflammatory disorders of the intestine, mainly including ulcerative colitis (UC) and Crohn’s disease (CD). These conditions usually present wit...
Inflammatory bowel disease (IBD) refers to a group of chronic and recurrent inflammatory disorders of the intestine, mainly including ulcerative colitis (UC) and Crohn’s disease (CD). These conditions usually present with abdominal pain, diarrhea, hematochezia, and weight loss, and may also lead to systemic complications. The pathogenesis of IBD is not fully understood but involves complex interactions among genetic predisposition, immune dysregulation, environmental factors, and intestinal microbiota changes. This review summarizes current knowledge of metal metabolism disorders in patients with IBD, with a focus on iron (Fe), copper (Cu), calcium (Ca), magnesium (Mg), zinc (Zn), and manganese (Mn), and their associations with IBD. It also examines the role of metal metabolism disorders in IBD pathogenesis and explores potential therapeutic strategies. Approaches such as inhibition of ferroptosis, regulation of copper homeostasis, modulation of calcium channels, and supplementation with magnesium and zinc, as well as adjustment of manganese metabolism, have been proposed to improve outcomes in IBD. In addition, the review highlights potential therapeutic roles of biological agents and nanomaterials, emphasizing their mechanisms through the regulation of metal metabolism.
Prevalence and clinical associations of anti-rods and rings antibodies in ANA-tested patients.
Can B, Ilki AA
Immunol Res · 2026 Feb · PMID 41712038 · Full text
Anti-rods and rings (anti-RR) antibodies represent a rare cytoplasmic antinuclear antibody (ANA) pattern typically associated with hepatitis C virus (HCV) infection and interferon-based therapy. However, emerging evidenc...
Anti-rods and rings (anti-RR) antibodies represent a rare cytoplasmic antinuclear antibody (ANA) pattern typically associated with hepatitis C virus (HCV) infection and interferon-based therapy. However, emerging evidence suggests a broader clinical relevance beyond HCV. This study aimed to investigate the prevalence, immunofluorescence characteristics, autoantibody associations, and clinical contexts of anti-RR antibodies in a large Turkish patient cohort undergoing routine ANA screening. Serum samples were retrospectively analysed for ANA using indirect immunofluorescence (IIF) between January 2022 and October 2024. Samples displaying anti-RR patterns were further evaluated for specific ANA profiles using line immunoassay. Clinical and demographic data were collected from medical records. Among 57,644 patients tested for ANA, 11,752 (20.39%) were ANA-positive, with only 91 cases (0.16%) exhibiting an anti-RR pattern. These cases were predominantly female (60.44%) with a median age of 52 years. Isolated anti-RR patterns were observed in 70.33% of patients, while the remainder showed mixed patterns, most commonly with AC-4,5,31 and AC-1 ANA patterns. Anti-RR positivity showed no significant association with classical ANA-specific autoantibodies. Clinically, anti-RR-positive patients displayed diverse diagnoses, including autoimmune diseases (21.98%), nephropathic conditions (9.89%), hepatic (7.69%) and pulmonary (6.59%) disorders, with the majority (53.85%) categorized under other conditions. Anti-RR antibodies, while rare, occur across a spectrum of diseases and may be associated with heterogeneous clinical conditions beyond hepatitis C infection. Their detection warrants careful interpretation within the appropriate clinical and laboratory context. Prospective studies are needed to explore their pathophysiological roles and diagnostic utility in diverse patient populations.
Elevated levels of advanced glycation end-products AGE10 in patients with reactive arthritis caused by Chlamydia trachomatis and Epstein-Barr virus infection.
Kril I, Zubchenko S, Havrylyuk A … +5 more , Lomikovska M, Kuzan A, Jaskuła E, Chopyak V, Gamian A
Immunol Res · 2026 Feb · PMID 41699165 · Full text
Advanced glycation end products (AGEs), and particularly the unique AGE10 epitope, may be a potential biomarker of immunopathology in rheumatic diseases. They may be associated with inflammation, joint damage and ossific...
Advanced glycation end products (AGEs), and particularly the unique AGE10 epitope, may be a potential biomarker of immunopathology in rheumatic diseases. They may be associated with inflammation, joint damage and ossification processes. AGE10 present in human and animal tissues could be detected with monoclonal antibody against melibiose-derived glycation product MAGE synthesized in anhydrous conditions. This MAGE product was different from the classic synthesis in water solution. The epitope was determined in serum with ELISA using these anti-MAGE monoclonal antibodies. This work aims to determine serum AGE10 levels in patients with reactive arthritis (ReA)-caused with Chlamydia trachomatis (group 2) and ReA with C. trachomatis during the reactivation of EBV infection (group 3). Additionally, ankylosing spondylitis (AS) patients (group 4) were involved in the study, due to the potential evolution of ReA toward AS. The control group maintained physiological AGE10 levels (316 µg/ml), while the combined infection group showed elevated AGE10 (850 µg/ml) compared to the chlamydial-only group (17 µg/ml). Fluorescent fAGE were at the highest level in AS patients. A striking finding was the complete absence of detectable AGE10 antigen in the AS group, coinciding with notably elevated immune complex AGE10-anti-AGE10 levels. A similar pattern was observed in patients with ReA caused by C. trachomatis alone (Group 2), albeit to a lesser extent. In contrast, both the control group and patients with ReA associated with EBV coinfection (group 3) displayed an inverse relationship, characterized by higher antigen levels and lower immune complex concentrations. Thus, diminished level of AGE10 could be caused, besides local accumulation, also by immune complexes formation, a pathogenic factor. Therefore, evaluating disease activity in ReA and AS is crucial to further our understanding of the pathophysiology of AGEs formation and predicting prognosis.
Innate lymphoid cells: unsung heroes or villains in multiple sclerosis pathogenesis?
Aliyu M, Saboor-Yaraghi AA, Sahraian MA … +4 more , Noorbakhsh F, Adamu AY, Sharif AA, Abdulqadir ZA
Immunol Res · 2026 Feb · PMID 41680537 · Publisher ↗
The emerging role of Innate Lymphoid Cells (ILCs) in the pathogenesis and regulation of Multiple Sclerosis (MS), a complex neuroinflammatory autoimmune disease, has been increasingly recognized. Once identified only for...
The emerging role of Innate Lymphoid Cells (ILCs) in the pathogenesis and regulation of Multiple Sclerosis (MS), a complex neuroinflammatory autoimmune disease, has been increasingly recognized. Once identified only for activities conducted at barrier surfaces, ILCs are now understood to be important modulators of inflammation and tissue repair within the Central Nervous System (CNS). This review aims to elucidate the 'two sides of the coin' nature of ILCs in MS. ILCs are implicated in pathogenesis by driving neuroinflammation through pro-inflammatory cytokines, contributing to the formation of ectopic meningeal lymphoid follicles, and modulating meningeal immune system interactions. In contrast, certain ILC subsets confer protective effects by secreting anti-inflammatory cytokines and promoting tissue homeostasis. Recent experimental and clinical studies have demonstrated the complex balance and alteration of ILC responsiveness at various stages of MS. We focused on the importance of ILC subset determination, including their dependence on key cytokine signaling pathways and their critical role in the gut-CNS axis, a pivotal mediator of systemic immunity in MS. Moreover, the potential for ILC pathway targeting, either by modulating cytokine networks or modifying the microbiota, is discussed as a promising avenue for restoring immune balance, promoting neuroprotection and suppressing ILC-driven inflammation. Despite the challenges presented by ILC plasticity and diversity, elucidating ILC biology offers a clear path toward developing precise immunomodulatory strategies aimed at halting disease progression and promoting CNS repair in patients with MS.
Rare KDM4C variants and reduced expression underlie epigenetic dysregulation in rheumatoid arthritis.
Oner DA, Toktas H, Dundar U … +2 more , Adar S, Eyvaz N
Immunol Res · 2026 Feb · PMID 41680357 · Full text
This study aims to investigate structural and expression-level alterations in the histone demethylase KDM4C gene in patients with rheumatoid arthritis (RA) and elucidate its role in the disease's epigenetic basis. KDM4C...
This study aims to investigate structural and expression-level alterations in the histone demethylase KDM4C gene in patients with rheumatoid arthritis (RA) and elucidate its role in the disease's epigenetic basis. KDM4C sequencing was performed in RA patients, and identified variants were mapped to functional domains, including the JmjN and PHD-type2 regions. KDM4C expression was assessed by quantitative PCR in RA and control groups. Molecular findings were analyzed alongside patients' clinical characteristics and treatment histories. A rare missense mutation (c.79 C > T, R27W) located in the JmjN domain was detected in a single patient with RA. In addition, a synonymous variant was identified in the PHD-type2 domain. The R27W variant is predicted by in silico analyses to impair protein homodimerization, while the synonymous change has been hypothesized to influence translational efficiency. Neither variant has previously been linked to RA. KDM4C mRNA expression was significantly reduced in patients with RA. This reduction was particularly evident in individuals with high CRP/ESR levels, positive RF and anti-CCP status, and treatment resistance. Taken together, the molecular and clinical findings suggest a potential functional alteration of KDM4C activity. Specifically, KDM4C may have a reduced capacity to remove repressive methylation marks on histone H3, particularly H3K9me3. These findings suggest that KDM4C dysregulation may promote a closed chromatin conformation in immune cells. This state may lead to silencing of genes involved in immune regulation and increased expression of inflammatory genes, thereby contributing to the pathogenesis of RA. KDM4C appears to be an important epigenetic regulator in RA pathogenesis. The coexistence of structural variants and decreased expression underscores its potential as a diagnostic biomarker and therapeutic target. To our knowledge, this is the first study providing integrated clinical and genetic evidence linking KDM4C dysregulation to RA.
miR-452-5p promotes systemic lupus erythematosus-induced inflammatory responses by downregulating RBL2 and impairing Treg development.
Zhai X, Gui F, Cen M … +1 more , Li S
Immunol Res · 2026 Feb · PMID 41667780 · Publisher ↗
Systemic lupus erythematosus (SLE) is a complex autoimmune disease. Studies have reported that miR-452-5p is highly expressed in SLE, while RBL2 is downregulated. This study aims to investigate the diagnostic value of mi...
Systemic lupus erythematosus (SLE) is a complex autoimmune disease. Studies have reported that miR-452-5p is highly expressed in SLE, while RBL2 is downregulated. This study aims to investigate the diagnostic value of miR-452-5p in distinguishing healthy controls from SLE patients and its potential regulatory mechanisms in SLE. A total of 114 patients with SLE were included in this study. The expressions of miR-452-5p, RBL2, Foxp3, CD4, CD25, RORC and IL-17 A were detected by RT-qPCR. The diagnostic value of miR-452-5p was analyzed by ROC. Cell detection included proliferation and apoptosis experiments, which were determined by CCK-8 method and flow cytometry respectively. ELISA was used to determine the contents of IFN-γ, TNF-α, IL-6, TGF-β1 and IL-10 in the cell supernatant. DLR verified the binding relationship between miR-452-5p and RBL2. Compared with the healthy control group, the expression of miR-452-5p was upregulated. Its diagnostic value for SLE reaches 0.902. miR-452-5p targets and regulates RBL2. Excessive proliferation of PBMCs, reduced apoptosis and imbalance of Treg/Th17. After inhibiting miR-452-5p, the RBL2 level increased, the PBMC proliferation decreased, and apoptosis increased. The Treg marker genes Fxop3, CD4 and CD25 levels increased, while the Th17 marker genes RORC and IL-17 A levels decreased. Inhibiting RBL2 can reverse the above changes. miR-452-5p is expected to become a novel biomarker for SLE. miR-452-5p may affect the proliferation and apoptosis of PBMC and the balance of Treg/Th17 cells by targeting RBL2 mRNA, and participate in the immunopathological process of SLE.
Shifts in immunometabolism in autoimmune diseases.
Mantri SS, Doshi GM
Immunol Res · 2026 Feb · PMID 41653355 · Publisher ↗
The immune system targets its own tissues in autoimmune disorders, chronic inflammatory syndromes that cause progressive damage and organ dysfunction. Psoriasis, multiple sclerosis, rheumatoid arthritis, and systemic lup...
The immune system targets its own tissues in autoimmune disorders, chronic inflammatory syndromes that cause progressive damage and organ dysfunction. Psoriasis, multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosus are amongst the conditions that are fuelled by excessive production of pro-inflammatory cytokines such as Tumor necrosis factor α (TNF-α), Interleukin 6 (IL-6), and Interleukin 17 (IL-17), as well as aberrant immune activation. Immunometabolism refers to the study of how metabolic pathways control immune cell activity and is associated with autoimmunity. The metabolic reprogramming that occurs during activation causes immune cells, including T cells, B cells, and macrophages, to switch from oxidative phosphorylation to glycolysis or glutaminolysis, which promotes increased cytokine release and rapid proliferation. In addition to maintaining the inflammatory response, this metabolic shift modulates the equilibrium between effector and regulatory cells, which increases autoimmunity. The chronic inflammation that characterizes autoimmune disorders is caused by the overproduction of cytokines in this altered metabolic state. This review offers fresh insights into the pathophysiology of autoimmunity by highlighting the importance of metabolic reprogramming in immune cells and its role in regulating cytokine production. Comprehensive insights into the metabolic pathway would reveal treatment opportunities that may help regulate abnormal cytokines and restore immunological balance.
Expression of key genes in IVIG-unresponsive Kawasaki disease and their immune correlation based on bioinformatics analysis.
Zhao ZH, Yang XY, Zhang H … +2 more , Li SJ, Li Y
Immunol Res · 2026 Jan · PMID 41575683 · Publisher ↗
This study employed bioinformatics to analyze the gene expression profile of Kawasaki disease (KD) patients and identify key genes associated with intravenous immunoglobulin (IVIG) non-response. The aim was to elucidate...
This study employed bioinformatics to analyze the gene expression profile of Kawasaki disease (KD) patients and identify key genes associated with intravenous immunoglobulin (IVIG) non-response. The aim was to elucidate the pathogenesis of IVIG non-responsive KD and identify potential predictive biomarkers and therapeutic targets. Gene expression datasets GSE48498 and GSE16797 were analyzed. Key steps included differential expression analysis, functional enrichment (GO/KEGG), weighted gene co-expression network analysis (WGCNA), immune cell infiltration analysis (CIBERSORT), protein-protein interaction (PPI) network construction, and machine learning algorithms (LASSO regression and random forest). Findings were validated using RT-qPCR. Differential expression analysis identified 327 differentially expressed genes (DEGs), enriched primarily in immune-related pathways. WGCNA revealed that the cyan and yellow modules exhibited a positive correlation with neutrophil and M0 macrophage infiltration levels. Integration of PPI networks, least absolute shrinkage and selection operator (LASSO) regression, and random forest algorithms identified CXCR1, FPR2, and MMP25 as core genes. Receiver operating characteristic (ROC) analysis yielded area under the curve (AUC) values of 0.887, 0.869, and 0.869 for CXCR1, FPR2, and MMP25, respectively; the combined diagnostic efficacy reached an AUC of 0.905. RT-qPCR validation confirmed significantly higher expression levels of CXCR1 and FPR2 in the IVIG non-responder group compared to responders (P < 0.05), while MMP25 expression showed no significant difference between groups. This study, combining bioinformatics analysis with experimental validation, identifies CXCR1 and FPR2 as key genes implicated in IVIG non-responsive KD.
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