Ghaderpanah R, van Beuningen F, Lin Y
… +6 more, Sadrian SH, Reijneveld HM, Krabbe H, Jonkheijm P, Bouma HR, Mankowski RT
Immunol Lett
· 2026 Feb · PMID 40845932
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Sepsis remains a major cause of mortality worldwide, driven by a dysregulated host response to infection that leads to life-threatening organ dysfunction. Despite advances in evidence-based medicine, early diagnosis and...Sepsis remains a major cause of mortality worldwide, driven by a dysregulated host response to infection that leads to life-threatening organ dysfunction. Despite advances in evidence-based medicine, early diagnosis and risk stratification remain significant challenges due to the complex, multifaceted nature of sepsis and substantial interindividual variability in clinical presentation. Current approaches relying on single biomarkers cannot provide comprehensive insights into disease progression, limiting their clinical utility in guiding timely and effective interventions. Given the limitations of current single biomarkers in capturing the complexity of sepsis, there is an urgent need for improved diagnostic approaches. While the discovery of novel biomarkers remains important, combining existing biomarkers may offer a pragmatic and effective strategy to improve diagnostic accuracy by leveraging the strengths of each to compensate for the limitations of other. In this clinical perspective, we highlight the potential of such combined biomarker strategies to enhance diagnostic accuracy, support identification of the infection source, and improve prognostic assessment across the clinical course and into long-term outcomes. We provide examples of key biomarkers and their synergistic potential, emphasizing the need for advanced analytical methods such as machine learning and multi-omics integration to enhance predictive accuracy. Shifting toward multi-component biomarker panels represents a critical step toward a more precise, personalized approach to sepsis management to reduce sepsis-related morbidity and mortality. We advocate for further research and validation efforts to facilitate the clinical implementation of combined biomarker models, ultimately transforming sepsis care.
Yanikoglu RS, Hekimoglu R, Celikten M
… +6 more, Yıldız Pekoz A, Gurol AO, Esrefoglu M, Akev N, Yılmaz Ozden T, Goncu B
Immunol Lett
· 2025 Dec · PMID 40803639
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Aloe vera, known for its rich phytochemical content, has long been used in traditional medicine. This study aimed to enhance its anti-inflammatory and anti-allergic properties by formulating an intranasal Aloe vera gel w...Aloe vera, known for its rich phytochemical content, has long been used in traditional medicine. This study aimed to enhance its anti-inflammatory and anti-allergic properties by formulating an intranasal Aloe vera gel with propylene glycol (PgAv) and assessing its efficacy through in vitro and in vivo models. In vitro, PgAv and Aloe vera gel (Av) were tested on LPS-induced HSAEC cells for mRNA expressions of TNFα, IL6, IL1β, and IL5. Co-culture experiments revealed PgAv reduced TNFα and increased IFNγ, promoting a T1-type response. In vivo, PgAv was administered intranasally to BALB/c mice with OVA-induced allergic airway inflammation model (AIAR). PgAv reduced mRNA expression of pro-inflammatory cytokines in bronchoalveolar lavage fluid (BAL), decreased TNFα and OVA-IgE levels in plasma, and attenuated eosinophil infiltration and lung inflammation. While PgAv increased IL6 levels, it concurrently reduced PGD2 levels, indicating a therapeutic effect via prostanoid synthesis pathways. PgAv demonstrated superior efficacy compared to Av in modulating inflammatory responses, enhancing T1 responses for immunological balance, and mitigating T2-mediated inflammation. These findings suggest PgAv as a promising treatment for allergic airway inflammation, warranting further investigation to clarify the underlying mechanisms.
Immunol Lett
· 2026 Feb · PMID 40784441
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Psoriasis is a systemic inflammatory disorder that has a significant impact on the quality of life of patients. E74-like factor 3 (ELF3) is a common transcriptional mediator of inflammation, but the effect of ELF3 on pso...Psoriasis is a systemic inflammatory disorder that has a significant impact on the quality of life of patients. E74-like factor 3 (ELF3) is a common transcriptional mediator of inflammation, but the effect of ELF3 on psoriasis development and severity is poorly understood. In this study, we first collected clinical normal skin tissues and skin tissues of psoriasis patients to detect the mRNA and protein levels of ELF3 and found that ELF3 was highly expressed in psoriasis skin tissues. We further used the imiquimod (IMQ)-induced mice model to mimic the phenotypic changes of human psoriasis in vivo, which are manifested as scaling, epidermal hyperplasia, and erythema formation, but knockdown of ELF3 resulted in suppression of these phenomena. In addition, downregulation of ELF3 expression inhibited neoangiogenesis and inflammatory cell infiltration. On this basis, we further found that ELF3 promotes the proliferation, angiogenesis, and inflammatory response of human keratinocyte HaCaT in vitro. Mechanistically, we found that ELF3 transcriptionally activated the activity of the downstream factor ADAM metallopeptidase domain 8 (ADAM8) by dual luciferase assays, thereby exacerbating the severity of psoriasis. We concluded that ELF3 is a key target for exacerbating psoriasis pathologic manifestations and promoting disease progression.
Immunol Lett
· 2025 Dec · PMID 40783085
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Inborn errors of immunity (IEI), traditionally known as primary immunodeficiencies, are genetically driven disorders that impair immune function. Emerging evidence suggests a strong connection between IEI and metabolic s...Inborn errors of immunity (IEI), traditionally known as primary immunodeficiencies, are genetically driven disorders that impair immune function. Emerging evidence suggests a strong connection between IEI and metabolic syndrome, including obesity, insulin resistance, and cardiovascular diseases, highlighting the complex interplay between immune and metabolic pathways. This review focuses on how changes in key immune regulatory genes can lead to both immune dysfunction and metabolic problems. Genome Wide Association Studies (GWAS) and Next Generation Sequencing (NGS) have identified numerous genetic variants that link immune and metabolic dysregulation. Both immune system dysfunction and metabolic imbalances are associated with mutations in several key genes such as STAT3, NLRP3, and FOXP3. Pharmacological interventions targeting inflammatory pathways, such as cytokine inhibitors and inflammasome modulators, offer promising therapeutic strategies to address both aspects of these intertwined conditions. Moreover, lifestyle modifications, including anti-inflammatory diets and physical activity, are essential components of a comprehensive approach to mitigate inflammation and improve metabolic outcomes. Advances in genomic profiling drive precision medicine, enabling the tailoring of treatments based on individual genetic variants, optimizing therapy for both immune and metabolic dysfunction. Personalized risk assessments incorporating genetic data further refine preventive strategies for metabolic syndrome. This cited approach underscores the importance of a holistic, integrated approach to unraveling the shared mechanisms of immune and metabolic dysregulation, offering insights into novel diagnostic and therapeutic strategies for these multifactorial disorders.
Nakamura S, Okamoto Y, Takada H
… +2 more, Katsumata Y, Harigai M
Immunol Lett
· 2025 Dec · PMID 40780484
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OBJECTIVES: To investigate the cytokine induction profile across multiple myeloid lineages by sera from patients with systemic lupus erythematosus (SLE) or polymyositis/dermatomyositis (PM/DM) using ex vivo whole blood s...OBJECTIVES: To investigate the cytokine induction profile across multiple myeloid lineages by sera from patients with systemic lupus erythematosus (SLE) or polymyositis/dermatomyositis (PM/DM) using ex vivo whole blood stimulation assay and identify the signaling pathway relevant to monocyte cytokine signature. METHODS: Serum samples were obtained from adult patients with SLE, anti-melanoma differentiation-associated gene 5 (MDA5)-positive DM, anti-aminoacyl tRNA synthetase (ARS)-positive PM/DM, and healthy controls. Heparinized whole blood from healthy donors was incubated with serum, IFN-α, and IFN-β, followed by flow cytometric analysis. The expression of 9 cytokines was analyzed in CD14 monocytes. The effect of upadacitinib preincubation on cytokine induction was evaluated. CD14 monocytes isolated from healthy donors were incubated with serum or IFN-β, followed by bulk RNA sequencing. RESULTS: Active SLE and MDA5 sera induced a shared monocyte cytokine signature with upregulation of monocyte chemoattractant protein-1 (MCP1) and interleukin-1 receptor antagonist (IL-1RA) in CD14 monocytes, whereas ARS and control sera did not. This monocyte cytokine signature closely resembled that induced by IFN-α and IFN-β. RNA-seq revealed 383 upregulated genes common to SLE serum, MDA5 serum, and IFN-β. Pathway analysis revealed that genes upregulated by exposure to SLE serum and MDA5 serum were predominantly involved in IFN-αβ signaling pathway. Upadacitinib abrogated the monocyte cytokine signature induced by SLE or MDA5 serum. CONCLUSIONS: Serum from patients with active SLE and anti-MDA5+ DM can induce a shared monocyte cytokine signature, primarily through the IFN-αβ signaling pathway. CD14 monocytes "primed" by serum may contribute to the pathogenesis of these diseases.
Nóbrega IS, Moysés MBB, Yokota-Moreno BY
… +3 more, Ferreira GG, Cebinelli GM, Sertié AL
Immunol Lett
· 2025 Dec · PMID 40752823
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Beyond its canonical role in innate immunity, the complement system (CS) has been increasingly implicated in brain development and disease. Elevated expression of complement component C4, in particular, is strongly assoc...Beyond its canonical role in innate immunity, the complement system (CS) has been increasingly implicated in brain development and disease. Elevated expression of complement component C4, in particular, is strongly associated with an increased risk of schizophrenia (SCZ), potentially by promoting excessive synaptic pruning. Astrocytes, the primary producers of CS components in the brain and expressers of multiple CS receptors, play crucial roles in synaptic formation and refinement. Dysregulated C4 levels may therefore impair astrocyte function, disrupt synaptic development, and contribute to SCZ pathogenesis. In this study, we investigated the direct effects of exogenous C4 on astrocyte differentiation, maturation, and reactivity using human induced pluripotent stem cell (hiPSC)-derived astrocytes. Astrocytes were treated with recombinant human C4 protein either chronically during differentiation or acutely after maturation. While chronic C4 exposure did not significantly affect astrocyte differentiation, both treatment regimens induced phenotypic features of astrocyte maturation and reactivity. These included upregulation of reactive astrocyte markers (CD44 and GFAP), morphological changes consistent with mature and reactive states, and nuclear translocation of NF-κB. Mechanistically, these effects may be mediated, at least in part, by activation of the MAPK/ERK pathway and suppression of mTORC1 signaling. Together, our findings suggest that elevated C4 levels promote astrocyte maturation and reactivity, providing new insights into the mechanisms by which complement dysregulation may contribute to SCZ pathogenesis.
Immunol Lett
· 2025 Dec · PMID 40749982
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The discovery of Tertiary Lymphoid Structures (TLS) within tumors has reshaped our understanding of cancer immunity. Unlike the classical view that immune responses are solely initiated in lymph nodes, TLS, ectopic lymph...The discovery of Tertiary Lymphoid Structures (TLS) within tumors has reshaped our understanding of cancer immunity. Unlike the classical view that immune responses are solely initiated in lymph nodes, TLS, ectopic lymphoid aggregates resembling secondary lymphoid organs, can form in the tumor microenvironment (TME). These structures contain T cells, B cells, dendritic cells (DC) presenting antigenic peptides to T cells in the T cell zone of TLS, and follicular dendritic cells (FDC) which are stromal cells involved in the formation of germinal centers (GCs) and presenting antigens, under the form of immune complexes, to B cells. Mature TLS with GCs support B cell differentiation into antibody-producing plasma cells (PCs). Clinical studies reveal that TLS presence correlates with improved survival and response to immunotherapy across multiple cancers, including melanoma, NSCLC, and renal cell carcinoma. Notably, B cells within TLS undergo clonal expansion, somatic hypermutation, and isotype switching, generating tumor-reactive antibodies (IgG, IgA). IgG-opsonized tumor cells can be eliminated by macrophages or NK cells via antibody-dependent cell mediated cytotoxicity or apoptosis by macrophages via antibody-dependent phagocytosis whereas IgA may have dual roles, sometimes promoting immunosuppression. Additionally, B cells enhance antigen presentation to T cells, amplifying anti-tumor responses. Emerging strategies aim to induce TLS formation (e.g., via CXCL13, lymphotoxins…) or harness B cells for adoptive therapies. Future research should clarify tumor-specific antibody targets and optimize TLS induction to enhance immunotherapy. In summary, TLS and B cells are pivotal in shaping anti-tumor immunity, offering novel biomarkers and therapeutic avenues for cancer treatment.
Montiel-Esparza R, Hawes I, Perriman R
… +6 more, Barbarito G, Oppizzi L, Shyr D, Kent L, Yao Z, Bertaina A
Immunol Lett
· 2025 Dec · PMID 40675223
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The validated Mount Sinai Acute graft-versus-host disease (aGvHD) International Consortium (MAGIC) algorithm and biomarker panels did not predict aGvHD occurrence or severity in pediatric αβT-cell/CD19 B-cell depleted ha...The validated Mount Sinai Acute graft-versus-host disease (aGvHD) International Consortium (MAGIC) algorithm and biomarker panels did not predict aGvHD occurrence or severity in pediatric αβT-cell/CD19 B-cell depleted haploidentical hematopoietic stem cell transplant (αβhaplo-HSCT) recipients. These findings suggest distinct aGvHD biology in the αβhaplo-HSCT setting, supporting the need for tailored biomarker studies in this unique transplant platform.
Immunol Lett
· 2025 Dec · PMID 40664317
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Innate antiviral immune pathways (InAIPs) are dysregulated in islets of type 1 diabetes (T1D) patients, implying how enterovirus might contribute to beta-cell autoimmunity. However, it is unclear whether similar dysregul...Innate antiviral immune pathways (InAIPs) are dysregulated in islets of type 1 diabetes (T1D) patients, implying how enterovirus might contribute to beta-cell autoimmunity. However, it is unclear whether similar dysregulation occurs in the intestine, contributing to pathologies like barrier dysfunction. Thus, we used a published genome-wide association study to identify polymorphisms in intestinal permeability and InAIP genes. We compared female prediabetic non-obese diabetic (NOD) and C57BL/6 mice and their jejunal epithelial RNA profile by GeneChip analysis. The potential link between dysregulation of InAIP genes and increased intestinal permeability was assessed by measuring trans-epithelial electrical resistance in intestinal Caco-2 cells upon R837 toll-like receptor 7 stimulation. There was genetic predisposition to T1D among intestinal permeability genes. However, InAIP genes contained more promising T1D-associated polymorphisms, especially for TNFA, OAS3, PIGR, CD55, NOD2, and IFIH1. Comparing prediabetic NOD with C57BL/6 mice revealed age-dependent dysregulation of several InAIP genes (Ifih1, Rnase1 etc.) in jejunum. Lastly, mimicking an enterovirus infection with R837 stimulation of Caco-2 cells increased intestinal permeability. We demonstrate genetic and transcriptional dysregulation of InAIPs in T1D and their potential involvement in intestinal barrier dysfunction, providing new clues to the disease-manifesting mechanisms of enterovirus infection.
Yang L, Liu S, Qiu C
… +3 more, Zhang Q, Zhang C, Jin Z
Immunol Lett
· 2025 Dec · PMID 40653057
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Interleukin-36 (IL-36) signaling pathway plays an important regulatory role in inflammatory and infectious diseases. However, the modulatory function of IL-36 in CD8T cells that are involved in liver cirrhosis with spont...Interleukin-36 (IL-36) signaling pathway plays an important regulatory role in inflammatory and infectious diseases. However, the modulatory function of IL-36 in CD8T cells that are involved in liver cirrhosis with spontaneous bacterial peritonitis (SBP) has not been understood. Sixty-five liver cirrhotic patients (42 untainted ascites and 23 SBP patients) and 20 controls were included. IL-36 levels were measured by ELISA. CD8T cells were purified from ascites, and were stimulated with IL-36 receptor antagonist (IL-36RA). CD8T cells were co-cultured with HepG2 cells in direct contact and indirect contact manners. Target cell death and cytotoxic molecules levels were investigated to assess CD8T cell cytotoxicity. The immune-checkpoint molecules expressions on CD8T cells were measured by flow cytometry. There were no significant differences in IL-36alpha, IL-36beta, or IL-36gamma levels between untainted ascites and SBP patients. SBP patients had increased ascitic IL-36RA, which positively correlated with alanine aminotransferase and ascitic neutrophil count. IL-36RA stimulation did not affect CD8T cell proliferation, but dampened CD8T cell-induced cell death and proinflammatory cytokine secretions. Perforin and granzyme B productions were down-regulated in direct contact manner. IL-36RA stimulation promoted immune-checkpoint molecules expressions on CD8T cells. The present findings revealed that elevated ascitic IL-36RA might inhibit ascitic CD8T cell cytotoxicty in liver cirrhotic patients with SBP.
Guerra-Assunção JA, Chakravarty P, Pollara G
… +9 more, Venturini C, Mlozowa VS, Denis B, Nyirenda M, Lalloo DG, Noursadeghi M, Brown JS, Heyderman RS, Wall EC
Immunol Lett
· 2025 Dec · PMID 40633592
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Pneumococcal meningitis (PM) has persistently poor clinical outcomes, especially in sub-Saharan Africa. To better characterise the inflammatory response and identify factors associated with mortality we compared paired p...Pneumococcal meningitis (PM) has persistently poor clinical outcomes, especially in sub-Saharan Africa. To better characterise the inflammatory response and identify factors associated with mortality we compared paired peripheral blood and cerebrospinal fluid (CSF) transcriptomes before the initiation of antibiotics in Malawian adults with proven PM. Blood transcriptional profiles were obtained in 28 patients with PM, with simultaneous paired with CSF profiles available for 13 patients. 15/28 (52 %) patients died. Comparison of the transcriptome between CSF and blood compartments showed upregulation of 2293 differentially expressed genes in CSF and 909 in blood; enriched pathways in CSF included inflammasome activity and neutrophil migration/activation, contrasting with enrichment for pathways including platelet and endothelial activation, cell cycle, cytokine release and oxidative stress in the blood transcriptome. Comparison of CSF profiles between survivors and non-survivors revealed 1829 differentially expressed genes. Non-survivor CSF was enriched for multiple innate inflammatory pathways, including IL-17A and Type 1 interferons and proteolysis. In contrast, minimal transcriptomic differences between outcome groups were detected in blood. Inflammation in PM is characterised by compartmentalised responses in blood and CSF. Poorer outcomes are associated with an dysregulated innate immune host response to S. pneumoniae in the CSF compartment.
Marri L, Contini P, Ivaldi F
… +10 more, Schiavi C, Magnani O, Vassallo C, Guastalla A, Traversone N, Deraco D, Angelini C, Del Zotto G, De Palma R, De Maria A
Immunol Lett
· 2025 Dec · PMID 40619105
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BACKGROUND: Splenomegaly represents a frequent non-infectious manifestation in Common Variable Immunodeficiency (CVID) and associates with specific clinical and immunophenotypic characteristics. OBJECTIVE: To investigate...BACKGROUND: Splenomegaly represents a frequent non-infectious manifestation in Common Variable Immunodeficiency (CVID) and associates with specific clinical and immunophenotypic characteristics. OBJECTIVE: To investigate the association between splenomegaly, infections, and immunophenotype in CVID patients. METHODS: A cohort of 32 CVID patients (13 with splenomegaly) was enrolled. Infectious workup encompassed a detailed medical history and data derived from routine diagnostic assessments including specific virological analysis of blood and stool samples, and QuantiFERON assay for tuberculosis. Immunophenotype was assessed by multiparametric flow cytometry. Statistical analyses were performed using Prism and Jamovi software. RESULTS: CMV viraemia was detected in 40 % of splenomegalic CVID (sCVID) and was absent in non-sCVID patients. Of all infectious agents, CMV was the only one associated with splenomegaly (p = 0.009). The inclusion of CMV replication as a causative factor for splenomegaly in CVID is in line with the knowledge that splenomegaly is a hallmark of acute CMV infection and could help explain in the present CVID cohort 75 % of otherwise unexplained splenomegalies. Flow cytometric analysis in sCVID vs. non-sCVID confirmed decreases in NK cell numbers and activation, in circulating inflammatory precursors (LinCD16), and increased T cell activation as defined by HLA-DR/CD69/CD38 expression. CONCLUSION: Splenomegaly in CVID patients may associate also with CMV replication. The combined identification in CMV sCVID of NK cell, inflammatory precursor and T cell imbalances suggests a possible combined cellular defect at precursor level in a subset of sCVID patients. When integrated into everyday clinical management, CMV viraemia could become a useful additional parameter for patient characterization and stratification.
Pascoal C, Granjo P, Mexia P
… +8 more, Gallego D, Adubeiro Lourenço R, Sharma S, Pérez B, Castro-Caldas M, Grosso AR, Dos Reis Ferreira V, Videira PA
Immunol Lett
· 2025 Dec · PMID 40619104
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OBJECTIVE: In this study, we examined the molecular response of human skin fibroblasts to an inflammatory cytokine to evaluate their suitability as models for immunopathology research. METHODS: Skin fibroblasts were stim...OBJECTIVE: In this study, we examined the molecular response of human skin fibroblasts to an inflammatory cytokine to evaluate their suitability as models for immunopathology research. METHODS: Skin fibroblasts were stimulated with tumour necrosis factor (TNF)-α, and the transcriptome was profiled via RNA-Seq. The differentially expressed genes were screened to predict immunological pathways and interactions. The cytokines and signaling pathways were validated at protein level. Similarly to immune cells, TNF-α caused transcriptional and transductional changes in fibroblasts. RESULTS: Functional analysis revealed significant enrichment of TNF-α signaling and cell chemotaxis (normalized enrichment score = 2.59 and 3.42). We also detected enrichment of nuclear factor kappa B (NF-κB) target genes and NF-kB activation, confirmed by complete protein degradation of its inhibitor IκBa (p = 0.0019). The MAPK/ERK and p38 MAPK pathways were also activated. Finally, we observed significant secretion of proinflammatory cytokines and chemokines, such as interleukin 6 (p = 0.02), CXCL8 (p = 0.027), CCL2 (p = 0.028) and CCL5 (p = 0.016). CONCLUSION: This study advances the biological understanding of skin fibroblast responses to TNF-α, revealing their intracellular pathways and secretome. It discloses techniques for leveraging fibroblasts' potential as in vitro models to identify inflammatory drivers, particularly when alternative models are inaccessible.
Kokoglu A, Engin A, Gelmez MY
… +4 more, Cetin EA, Senel GB, Karadeniz D, Deniz G
Immunol Lett
· 2025 Dec · PMID 40602438
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Restless legs syndrome (RLS) is a sleep-related disorder, and some evidence suggests that inflammation contributes to its pathophysiology. This study aimed to investigate the relationship between RLS and immune cells. Fo...Restless legs syndrome (RLS) is a sleep-related disorder, and some evidence suggests that inflammation contributes to its pathophysiology. This study aimed to investigate the relationship between RLS and immune cells. Fourteen RLS patients, and 10 healthy subjects were included in the study. The percentages of T, B, natural killer (NK), natural killer T (NKT) and innate lymphoid cells (ILCs) were analyzed, along with intracellular levels of interferon-gamma (IFN-γ), interleukin (IL)-6, IL-10, and IL-13 in T, B and NK cells. Additionally, CD8 T and NK cell cytotoxic activities were assessed using flow cytometry. Plasma levels of IFN-γ, tumor necrosis factor-alpha (TNF-α), IL-2, IL-4, IL-6, IL-10, and IL-13 were evaluated with bead-based soluble molecule assay. Compared to healthy subjects, the ratio of ILC-1 subset and IL-13CD4 T cells were significantly increased in RLS patients, while the levels of ILC-2 subset were significantly decreased. When the NK cell cytotoxic activity of RLS patients was evaluated, it was found that the NK cell perforin levels were lower than healthy subjects. Plasma IL-13 levels were also significantly elevated in RLS patients compared to healthy individuals. These findings suggest that both innate and adaptive immune responses may play a role in RLS pathophysiology. Alterations in ILC subsets, along with elevated IL-13, IL-10, and IL-6 levels, as well as NK and CD8 T cell cytotoxic activity, indicate that immune dysregulation might contribute to the disease mechanism. Furthermore, the observed correlation between efficient sleep and immune markers highlights the potential role of immune system modulation in RLS management.
Hooda V, Sharma D, Singh A
… +4 more, Das D, Gupta S, Arava S, Sharma A
Immunol Lett
· 2025 Dec · PMID 40582577
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Innate immune cells, particularly natural killer (NK) cells and dendritic cells (DCs), play a crucial role in the immunopathogenesis of Pemphigus Vulgaris (PV), an autoimmune blistering disorder. Dysregulation of these i...Innate immune cells, particularly natural killer (NK) cells and dendritic cells (DCs), play a crucial role in the immunopathogenesis of Pemphigus Vulgaris (PV), an autoimmune blistering disorder. Dysregulation of these innate cells can lead to significant consequences in the adaptive immune response, contributing to disease progression. This study investigates the crosstalk between NK cells and DCs as a potential therapeutic target for PV. Our findings reveal an increased frequency of DCs (mDCs and pDCs) and NK cells (CD56 and CD56) in the peripheral circulation of PV patients. NK cells exhibited elevated granzyme activity and IFNγ production, while DCs displayed enhanced phagocytic capabilities. In vitro, we observed upregulated mRNA expression of potentially interacting co-stimulatory markers (CD40 and CD80) and chemokines (CXCL10 and CXCL8) in DCs, alongside increased expression of their corresponding receptors (CD40L, CD80L, CXCR3, and CXCR1) on NK cells. Lesional tissues from PV patients also showed heightened expression of these receptor-ligand pairs. Co-culture experiments further demonstrated increased granzyme activity in NK cells and enhanced phagocytosis in DCs, however, blocking of CXCR3 resulted in decreased granzyme activity, suggesting a functional modulation through their interaction. These findings highlight the significant role of NK-DC crosstalk in PV pathogenesis and suggest that targeting this interaction could offer a novel therapeutic strategy to modulate immune responses in PV, offering the potential for more effective treatment approaches.
Zhang Z, Chen J, Xiong Z
… +6 more, Lin W, Yang B, Zong Z, Shen B, Luo H, Liu C
Immunol Lett
· 2025 Dec · PMID 40543727
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OBJECTIVE: This study aims to analyse the expression of CD37 in different B cell subsets from human peripheral blood, exploring changes in CD37 expression in B cells of patients with primary Sjögren's syndrome (pSS) and...OBJECTIVE: This study aims to analyse the expression of CD37 in different B cell subsets from human peripheral blood, exploring changes in CD37 expression in B cells of patients with primary Sjögren's syndrome (pSS) and assessing their clinical relevance. METHODS: A total of 32 pSS patients and age- and sex-matched healthy controls were included. Peripheral blood mononuclear cells (PBMCs) were isolated, and B cells were classified into five subsets using flow cytometry based on CD24 and CD38 expression. CD37 expression was evaluated, and functional differences between CD37+ and CD37- B cells were compared. Peripheral lymphocytes were stimulated with LPS to observe changes in CD37 expression. The expression of CD37 and related B cell subsets was also compared between pSS patients and healthy controls, followed by ROC curve analysis. RESULTS: CD37 was highly expressed in early-stage B cells, with a significant decrease in effector cells. CD37+ B cells exhibited higher proportions of CD40+, HLA-DR+, and IL-10+ cells, indicating enhanced antigen-presenting and regulatory capabilities. Post-LPS stimulation, CD37 expression significantly declined in pSS patients compared to healthy controls, suggesting increased sensitivity to differentiation into plasma cells. Additionally, CD37-related B cell subsets in pSS patients showed strong correlations with autoantibodies and immunological markers. ROC analysis revealed substantial areas under the curve, confirming the diagnostic potential of these subsets. CONCLUSION: The expression of CD37 in B cell subsets is variable, indicating a potential regulatory role in B cell function and offering auxiliary diagnostic value in pSS.
Lu Q, van der Meeren LE, Eikmans M
… +1 more, van der Hoorn MLP
Immunol Lett
· 2025 Dec · PMID 40505778
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Chronic histiocytic intervillositis (CHI) is associated with adverse pregnancy outcome and results in placental inflammation characterized by maternal myeloid cells within the intervillous space. This intervillous space...Chronic histiocytic intervillositis (CHI) is associated with adverse pregnancy outcome and results in placental inflammation characterized by maternal myeloid cells within the intervillous space. This intervillous space is part of the maternal-fetal interface, which provides a unique microenvironment for the immunologic crosstalk between intervillous blood and placental components. The pathophysiologic pathways of CHI are still unclear. Here, we conduct a narrative review on the current knowledge about CHI, intervillous blood sampling methods, and immune cell characteristics in the intervillous space of healthy term pregnancy. We highlight that the detailed phenotype and functional investigation of maternal immune cells from intervillous blood of placentas with CHI is expected to provide better understanding of the etiology of disease.
Lores P, Costa M, Saravia A
… +11 more, Landeira M, da Costa V, Rodríguez-Zraquia SA, Cedrés ME, Oliva J, Rado G, García I, Festari MF, Consani S, Díaz C, Freire T
Immunol Lett
· 2025 Dec · PMID 40494406
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Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by severe joint inflammation, synovial hyperplasia and degradation of the cartilage and bone in the joint. Patients with RA have an amplified T help...Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by severe joint inflammation, synovial hyperplasia and degradation of the cartilage and bone in the joint. Patients with RA have an amplified T helper (Th) 1 and Th17 immune response and production of autoantibodies by autoreactive B cells. In the joint, macrophages mediate bone destruction and maintain the inflammatory process in RA. There is an increasing body of evidence indicating that NADPH oxidase (NOX2)-derived reactive oxygen species (ROS), mainly produced by macrophages and neutrophils, may have effector functions in RA. In this work we characterized ROS production in both monocytes and macrophages in RA. Our results indicate that NOX2-dependent production of ROS attenuates inflammation and clinical signs by decreasing innate and adaptive immune responses in collagen-induced arthritis in mice. We also report that ROS production by circulating classical and non-classical monocytes from patients with RA negatively correlate with disease symptoms. Therefore, ROS produced by different monocyte subsets in peripheral blood might be considered as useful biomarkers or predictors of the immune response associated with RA disease activity.