Immunology letters最新文献

{"title":"Quercetin improves macrophage immune regulatory functions to alleviate airway Th2 polarization","authors":"Yixuan Dong ,&nbsp;Le Liu ,&nbsp;Xiwen Zhang ,&nbsp;Haoyue Zheng ,&nbsp;Yu Liu ,&nbsp;Aizhi Zhang ,&nbsp;Lingzhi Xu ,&nbsp;Yuanyi Zhang ,&nbsp;Gui Yang ,&nbsp;Pingchang Yang","doi":"10.1016/j.imlet.2025.107030","DOIUrl":"10.1016/j.imlet.2025.107030","url":null,"abstract":"<div><h3>Background</h3><div>Th2 polarization is a central driver of allergic airway inflammation, yet the epigenetic mechanisms underlying its dysregulation remain poorly defined. Quercetin is a bioactive flavonoid with immunomodulatory properties. This study investigates whether quercetin alleviates Th2-driven pathology in allergic airway inflammation by targeting IL-10 promoter hypermethylation in airway M2 macrophages.</div></div><div><h3>Methods</h3><div>Using a murine model of house dust mite (Derf2)-induced allergic airway inflammation, we isolated airway M2 macrophages via flow cytometry and assessed their immunosuppressive capacity using CFSE-based T cell proliferation assays. Epigenetic regulation of <em>Il10</em> was analyzed by bisulfite sequencing and chromatin immunoprecipitation. Quercetin (intranasal) was administered daily for 7 days.</div></div><div><h3>Results</h3><div>Allergic mice exhibited impaired M2 cell-mediated T cell suppression (proliferation index: 85% vs. 34% in controls, P &lt; 0.01) and IL-10 deficiency in bronchoalveolar lavage fluid (8.5 pg/ml vs. 28.2 pg/ml, P &lt;0.001). Il10 promoter hypermethylation (72% vs. 35% methylation at CpG sites -200 to +100) and reduced KDM5A recruitment were observed in M2 cells from allergic mice. Quercetin treatment reversed these epigenetic defects, restoring KDM5A binding (P &lt; 0.05) and Il10 transcription (2.1-fold increase, P &lt; 0.01), thereby reducing Th2 cytokines and airway hyperresponsiveness.</div></div><div><h3>Conclusions</h3><div>Our findings identify KDM5A-mediated <em>Il10</em> promoter demethylation as a critical mechanism for M2 cell immunoregulation in allergic airway inflammation. Quercetin alleviates Th2-driven pathology by restoring Il10 expression via epigenetic reprogramming of M2 macrophages. This study advances the understanding of natural compounds in targeting epigenetic checkpoints and provides a rationale for quercetin-based therapies in allergic diseases.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"275 ","pages":"Article 107030"},"PeriodicalIF":3.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143899640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The immune-reinforcements of Lenvatinib plus anti-PD-1 and their rationale to unite with TACE for unresectable hepatocellular carcinoma treatment","authors":"Jiayun Jiang ,&nbsp;Hui Zhang ,&nbsp;Yanjiao Ou ,&nbsp;Jiejuan Lai ,&nbsp;Yulan Huang ,&nbsp;Wenyun Cai ,&nbsp;Chong Li ,&nbsp;Leida Zhang ,&nbsp;Yu Fu","doi":"10.1016/j.imlet.2025.107003","DOIUrl":"10.1016/j.imlet.2025.107003","url":null,"abstract":"<div><h3>Background</h3><div>Despite encouraging clinical benefits have gained by anti-PD-1 and Lenvatinib combination, in-depth characterizations about the mechanisms of action remain poorly characterized. Furthermore, although the combination of systemic anti-PD-1 or Lenvatinib treatment and locoregional transcatheter arterial chemoembolization (TACE) is widely carried out to treat unresectable HCC in clinical, the efficacies of different combination regimens are uncertain due to limited researches.</div></div><div><h3>Methods</h3><div>We firstly generated murine HCC models to validate the enhanced anti-tumor effects of anti-PD-1 and Lenvatinib combination therapy. Then single cell mass cytometry (CyTOF) was employed to phenotypically reveal their mechanisms of action. After that, we further compared the effectiveness of TACE plus Lenvatinib (i.e., TACE-Len) dual therapy with TACE, Lenvatinib plus anti-PD-1 (i.e., TACE-Len-PD-1) triple therapy as conversion therapy for unresectable HCC.</div></div><div><h3>Results</h3><div>Lenvatinib and anti-PD-1 combination could generate activated immune profiles not only by increasing systemic CD4⁺, CD8⁺ <em>T</em> cells and B cells proportions, but also by weakening the immune-tolerance functions derived from both immunosuppressive cells (i.e., MDSCs) and co-inhibitory mediators (i.e., PD-L1 and LAG-3). Meanwhile, our study also suggested that TACE-Len-PD-1 triple therapy could achieve better clinical responses with powerful immune profiles for unresectable HCC compared to TACE-Len dual therapy.</div></div><div><h3>Conclusions</h3><div>Our study provided a delicate immune landscape of anti-PD-1and Lenvatinib combination, and we also offered scientific evidences that TACE-Len-PD-1 triple therapy could fulfill better clinical benefits than TACE-Len dual therapy, which is anticipated to provide objective and effective evidences for clinical use.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"275 ","pages":"Article 107003"},"PeriodicalIF":3.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BENTA disease or CARD11 gain-of-function? A novel variant with atypical features and a literature review","authors":"Letizia Baldini ,&nbsp;Bärbel Keller ,&nbsp;Lisa Dewitte ,&nbsp;Chiara Passarelli ,&nbsp;Monia Ginevrino ,&nbsp;Diana Carli ,&nbsp;Davide Montin ,&nbsp;Xavier Bossuyt ,&nbsp;Klaus Warnatz ,&nbsp;Francesco Licciardi","doi":"10.1016/j.imlet.2025.107005","DOIUrl":"10.1016/j.imlet.2025.107005","url":null,"abstract":"<div><h3>Introduction</h3><div>The CARD11 (Caspase Recruitment Domain Family Member 11) gene encodes a scaffold protein critical for NF-κB signaling, regulating B-cell differentiation and T-cell effector functions. Gain-of-function (GOF) mutations in CARD11 cause BENTA disease (B cell Expansion with NF-κB and T cell Anergy), an autosomal dominant disorder typically presenting with early-onset polyclonal B-cell lymphocytosis, splenomegaly, lymphadenopathy, and recurrent infections.</div></div><div><h3>Methods</h3><div>We describe three related patients harboring a novel CARD11-GOF mutation (D357E), presenting with a BENTA phenotype with atypical features, including high IgM levels and a normal B-cell count, with life-threatening HLH in one case. Additionally, we conducted a systematic literature review using PubMed and EMBASE to identify previously reported cases of CARD11 GOF mutations.</div></div><div><h3>Results</h3><div><em>In vitro</em> functional analysis demonstrated that the D357E variant activates the NF-κB signaling pathway in primary lymphocytes and in HEK293T cells transfected with mutant CARD11. Our literature review identified 13 studies describing 29 patients. Notably, HLH emerged as a common complication of CARD11 GOF mutations (18.8 %), while B-lymphocytosis –though frequent– was not universally present.</div></div><div><h3>Conclusion</h3><div>We identified a novel pathogenic CARD11 variant and described its atypical phenotype, further expanding the clinical spectrum of CARD11 GOF disorders. These findings underscore the need for increased awareness of HLH risk in patients with CARD11 GOF mutations.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"275 ","pages":"Article 107005"},"PeriodicalIF":3.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD4+ T-cell help delivery to monocyte-derived dendritic cells promotes effector differentiation of helper and cytotoxic T cells","authors":"Douwe M. T. Bosma ,&nbsp;Julia Busselaar ,&nbsp;Mo D. Staal ,&nbsp;Elselien Frijlink ,&nbsp;Matthias Mack ,&nbsp;Fiamma Salerno ,&nbsp;Jannie Borst","doi":"10.1016/j.imlet.2025.107022","DOIUrl":"10.1016/j.imlet.2025.107022","url":null,"abstract":"<div><div>Delivery of CD4⁺ T-cell help optimizes CD8⁺ T-cell effector and memory responses via CD40-mediated licensing of conventional dendritic cells (DCs). Using comparative vaccination settings that prime CD8⁺ T cells in presence or absence of CD4⁺ T-cell help, we observed that CD4⁺ T-cell activation promoted influx of monocytes into the vaccine-draining lymph nodes (dLNs), where they differentiated into monocyte-derived (Mo)DCs, as defined by the most recent standards. Abrogation of these responses by CCR2-targeted depletion indicated that monocyte-derived cells in the dLN promoted T-helper 1 (Th1) type effector differentiation of CD4⁺ T cells, as well as effector differentiation of CD8⁺ T cells. Monocyte-derived cells in dLNs upregulated CD40, CD80 and PD-L1 as a result of CD4⁺ T-cell help. The response of monocyte-derived cells to CD4⁺ T-cell help was independent of natural killer (NK) cells and proceeded via CD40 ligand (L)-CD40 interactions and IFNγ signaling. Our data argue for a scenario wherein activated CD4⁺ T cells in dLNs crosstalk via CD40L and IFNγ signals to monocytes, promoting their local differentiation into MoDCs. This event enhances formation of CD4⁺ Th1 and CD8⁺ cytotoxic effector T cell pool, most likely by virtue of their improved costimulatory status and cytokine production.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"275 ","pages":"Article 107022"},"PeriodicalIF":3.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143877080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the hidden syndrome: The enigma of anti-transcobalamin receptor autoantibodies","authors":"Kazuki M. Matsuda,&nbsp;Hirohito Kotani,&nbsp;Shinichi Sato,&nbsp;Ayumi Yoshizaki","doi":"10.1016/j.imlet.2025.107028","DOIUrl":"10.1016/j.imlet.2025.107028","url":null,"abstract":"<div><div>The transcobalamin receptor (CD320) functions as a critical mediator for vitamin B12 uptake in cells, with emerging evidence linking autoantibodies against CD320 to various autoimmune conditions. Pluvinage et al.'s recent study identified anti-CD320 autoantibodies as a cause of autoimmune vitamin B12 central deficiency, specifically affecting the central nervous system while sparing peripheral nerves. Their findings align with our previous work showing anti-CD320′s role in cutaneous arteritis. Both studies identified overlapping CD320 epitopes targeted by autoantibodies and demonstrated the therapeutic efficacy of high-dose vitamin B12 supplementation in mitigating symptoms. Expanding on these findings, we observed anti-CD320 autoantibodies in other inflammatory disorders such as systemic sclerosis, suggesting a broader clinical relevance. The work by Pluvinage et al. and our group supports the concept of an \"anti-CD320-associated syndrome,\" with high-dose B12 supplementation as a promising treatment strategy. Further research is needed to fully elucidate the tissue-specific mechanisms and pathophysiology underlying these autoimmune conditions.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"275 ","pages":"Article 107028"},"PeriodicalIF":3.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143868766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Platelet-derived microvesicles modulate cytokine and lipid mediator profiles in THP-1 monocytes and macrophages","authors":"Robert D. Foulem ,&nbsp;Maroua Mbarik ,&nbsp;Jérémie A. Doiron ,&nbsp;Marie-France N. Soucy ,&nbsp;Dayana Toro-Ramirez ,&nbsp;Florient Pecourt ,&nbsp;David A. Barnett ,&nbsp;Luc H. Boudreau ,&nbsp;Marc E. Surette","doi":"10.1016/j.imlet.2025.107029","DOIUrl":"10.1016/j.imlet.2025.107029","url":null,"abstract":"<div><div>Monocytes are circulating immune cells that migrate to inflamed tissues and differentiate into macrophages, where they play a dual role in regulating pro-inflammatory and pro-resolving responses through cytokine and lipid mediator secretion. Platelet-derived microvesicles (PMVs), released during platelet activation, infiltrate inflamed areas and interact with monocytes and macrophages, facilitating the transfer of bioactive contents. While these interactions have been observed, their functional consequences on monocyte/macrophage inflammatory profiles remain poorly understood. In this study, PMVs are shown to be internalized by human THP-1 monocytes. The interaction with THP-1 cells occurs rapidly, with 60 % of cells interacting with PMVs within one hour. When cells are differentiated to M₀ and M₁ macrophages, interactions with PMVs only peak after 24 h. Interaction of cells with PMVs resulted in an increased capacity to synthesize cyclooxygenase- and lipoxygenase-derived lipid mediators of inflammation, especially in M₁ cells. Cytokine production was also influenced in a cell-state-dependent manner. PMVs had no impact on undifferentiated THP-1 cells but enhanced the production of several cytokines in M₀ cells as well as IL-23 and IL-6 in M₁ macrophages. When stimulated with lipopolysaccharides, PMV-treated M₀ macrophages demonstrated elevated production of the anti-inflammatory cytokine IL-10, while M1 macrophages exhibited increased secretion of IL-1β, MCP-1, and IL-6, highlighting an effect on pro-inflammatory cytokine production. These findings reveal that PMVs selectively modulate the inflammatory cytokine and lipid mediator profiles of monocytes and macrophages depending on their differentiation state. This study underscores the role of PMVs as key players in intercellular communication and immune regulation, particularly in the context of inflammation.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"275 ","pages":"Article 107029"},"PeriodicalIF":3.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143924637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel MF59 and CpG1018 adjuvant combination enhances the humoral and cellular immune responses against a truncated varicella-zoster viral glycoprotein E","authors":"Jing Yang ,&nbsp;Xue Hu ,&nbsp;Xiguang Chen ,&nbsp;Wanzhen Li ,&nbsp;Quanyi Yin ,&nbsp;Yelin Xiong ,&nbsp;Youcai An ,&nbsp;Haiyan Li ,&nbsp;Zhilei Liu","doi":"10.1016/j.imlet.2025.107025","DOIUrl":"10.1016/j.imlet.2025.107025","url":null,"abstract":"<div><div>Vaccination is the only effective strategy for preventing herpes zoster (HZ), a disease caused by reactivation of the varicella-zoster virus (VZV). Cell-mediated immunity (CMI) plays a pivotal role in controlling VZV reactivation and is a critical factor in the efficacy of the HZ vaccine. This research introduced the preliminary utilization of truncated glycoprotein E (tgE) as the antigen in the formulation of an innovative recombinant HZ vaccine and explored the combination of tgE with several adjuvants to assess their effectiveness in eliciting robust humoral and CMI responses in C57BL/6 mice, followed by the immunogenicity validation of the optimal vaccine formulation in Sprague-Dawley (SD) rats and cynomolgus monkeys. The results demonstrated that the combination of tgE with MF59 and CpG1018, designated as tgE/MF59+CpG1018, elicited significantly stronger gE-specific humoral and cellular immune responses in C57BL/6 mice compared to any single adjuvant or other adjuvant combinations. The optimal dosages for MF59 and CpG1018 were determined to be 0.025 ml and 10 μg, respectively, for each 0.05 ml of the vaccine formulation. Notably, the increasing in the dosage of the adjuvant does not inherently correlate with a more pronounced immune response. Furthermore, the tgE/MF59+CpG1018 also elicited robust humoral and CMI responses in both SD rats and cynomolgus monkeys. These findings established the novel tgE/MF59+CpG1018 vaccine as a highly promising prophylactic candidate against HZ.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"275 ","pages":"Article 107025"},"PeriodicalIF":3.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143839369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characteristics and specific differential gene analysis of the TCR immune repertoire in secondary adult HLH lymphocytes","authors":"Yongsheng Chen ,&nbsp;Wenrui Xiao ,&nbsp;Shiyi Yuan ,&nbsp;Cong Wang ,&nbsp;Meizhen Shi ,&nbsp;Dan Yu ,&nbsp;Ying Zhang ,&nbsp;Shifeng Lou","doi":"10.1016/j.imlet.2025.107023","DOIUrl":"10.1016/j.imlet.2025.107023","url":null,"abstract":"<div><h3>Background</h3><div>Hemophagocytic lymphohistiocytosis (HLH) is a severe, life-threatening, and hyperinflammatory disorder characterized by excessive immune activation and systemic immune dysregulation. Despite advancements in diagnosis, the underlying alterations in the immune repertoire in HLH remain poorly understood. This study aimed to characterize remodeling in the T cell receptor (TCR) immune repertoire in patients with HLH, focusing on V(D)J gene usage, complementarity-determining region 3 (CDR3) diversity, and clonotypic distribution, to better understand the immunological basis of the disease.</div></div><div><h3>Methods</h3><div>Thirty individuals were enrolled, including 16 untreated patients with HLH(U group), 4 patients with HLH undergoing post-induction therapy (T group), and 10 healthy controls (Hc group). Peripheral blood TCRβ sequencing was performed to analyze V(D)J gene usage, CDR3 length distribution, and repertoire diversity. The relative diversity index (RDI) and hierarchical clustering of V-J pairing frequencies were applied to evaluate immune repertoire alterations. Statistical analyses included one-way ANOVA and Wilcoxon rank-sum tests to assess group differences, with a significance threshold of <em>P</em> &lt; 0.05.</div></div><div><h3>Results</h3><div>Compared to healthy individuals, patients with HLH exhibited significant alterations in TCR diversity, including increased CDR3 length variability and shifts in V(D)J gene usage (<em>P</em> &lt; 0.05). In particular, TRBV5–1 and TRBJ2–7 expression was observed in patients with HLH. The V-J pairing analysis demonstrated that HLH samples clustered distinctly from healthy controls, suggesting immune dysregulation. RDI analysis revealed a significantly higher diversity in the M-HLH group than in the non-M-HLH group (<em>P</em> &lt; 0.05), indicating higher clonal expansion in the malignant subgroup. Following induction therapy, TCR diversity showed partial recovery (<em>P</em> &lt; 0.05);however, the immune repertoire remained distinct from that of healthy individuals (<em>P</em> &lt; 0.05).</div></div><div><h3>Conclusions</h3><div>HLH is associated with profound immune repertoire remodeling, particularly in V-J gene pairing and CDR3 diversity. The RDI values and significant differences in gene pairing suggest antigen-driven clonal expansion in patients with HLH. Immune repertoire profiling may act as an effective biomarker for HLH classification and disease monitoring. Further studies with larger cohorts and longitudinal data are required to validate these findings and explore their clinical application in HLH.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"275 ","pages":"Article 107023"},"PeriodicalIF":3.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143863843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Remdesivir alleviates joint damage in collagen-induced arthritis and inhibits inflammatory cell death of RA synovial fibroblasts","authors":"A Ram Lee ,&nbsp;Hong Ki Min ,&nbsp;Seon-Yeong Lee ,&nbsp;Su Been Jeon ,&nbsp;Chae Rim Lee ,&nbsp;Tae Ho Kim ,&nbsp;Jin Hyung Park ,&nbsp;Mi- La Cho","doi":"10.1016/j.imlet.2025.107009","DOIUrl":"10.1016/j.imlet.2025.107009","url":null,"abstract":"<div><h3>Background</h3><div>The antiviral agent, remdesivir, is adenosine analogue which is currently also used as anti-coronavirus disease 2019. Remdesivir also had anti-inflammatory effect which reduced pro-inflammatory cytokine production, and inhibition of the cyclic GMP-AMP synthase–STING pathway.</div></div><div><h3>Methods</h3><div>We evaluated the antiarthritic effects of remdesivir in a mouse model of High-fat diet (HFD) collagen-induced arthritis (CIA) and in fibroblast-like synoviocytes from patients with RA. Type II collagen was administered to DBA/1J mice to induce CIA. Vehicle or remdesivir was injected subcutaneously three times a week. During 7 weeks of treatment, the arthritis score and incidence were evaluated twice a week. Flow cytometry and confocal imaging were used to evaluate CD4 + T cells in the spleen. FLSs from patients with RA were stimulated <em>in vitro</em> with remdesivir and tumor necrosis factor (TNF)-α, and western blotting was used to measure the expression of STING and necroptosis-related markers.</div></div><div><h3>Results</h3><div>Remdesivir administration suppressed the incidence and progression of arthritis in mice with CIA. Histological analysis revealed lower inflammation and cartilage damage scores in remdesivir-treated than in vehicle groups. Interleukin (IL)-17 + CD4 + T-cell differentiation was inhibited in the remdesivir-treated group. Furthermore, IL-17/-6/-1β, monocyte chemoattractant protein -1, and TNF-α expression was reduced in the remdesivir group. <em>In vitro</em>, remdesivir suppressed the expression of STING, nuclear factor-κB, RIPK3, and phosphorylated MLKL in RA–FLSs under TNF-α stimulation.</div></div><div><h3>Conclusions</h3><div>The antiviral agent remdesivir suppressed arthritis by regulating Th cell differentiation, pro-inflammatory cytokine expression, the STING pathway, and necroptosis.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"275 ","pages":"Article 107009"},"PeriodicalIF":3.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Double positive IL-17A+IFN-γ+CCR6+ ILCs contribute towards the immunopathology of lepromatous leprosy","authors":"Chaman Saini ,&nbsp;Leena Sapra ,&nbsp;V. Ramesh ,&nbsp;Poonam Puri ,&nbsp;Rupesh K. Srivastava","doi":"10.1016/j.imlet.2025.107012","DOIUrl":"10.1016/j.imlet.2025.107012","url":null,"abstract":"<div><div>Leprosy is a skin disease caused by <em>Mycobacterium leprae</em>, characterized by both localized and generalized immune responses. Th1/17 lymphocytes play a crucial role in the immune response against <em>M. leprae</em>. However, adaptive immunity alone is not sufficient to completely eradicate the pathogen, suggesting the involvement of other innate immune cells in pathogen removal. Therefore, we investigated innate lymphoid cells (ILCs), which are the innate counterparts of helper T cells in adaptive immunity and are known to produce IFN-γ and IL-17. In the present study, we evaluated the expression of ILC1 and ILC3 in borderline tuberculoid (BT) and lepromatous leprosy (LL) lesional skin by flow cytometry and real time PCR. Further, the expression of various in-situ genes, including cytokines, chemokines, cytokine receptors chemokine receptors, and transcription factors by qPCR in skin lesions of leprosy patients were analyzed. The phenotypes of ILC1 and ILC3 cells were determined as CD3^negCCR6⁺CD19^negIFN-γ⁺ and CD3^negCCR6⁺CD19^negIL-17A⁺, respectively, by flow-cytometry analysis. BT skin lesions represents high CCR6⁺expression on total ILCs as compared to LL patients. Our results clearly indicate that ILC1 and ILC3 were highly expressed in skin lesions of BT as compared to LL leprosy patients. Moreover, we observed that double positive (DP) CD3^negCCR6⁺CD19^negIFN-γ⁺IL-17A⁺ ILCs were up-regulated in LL and showed a pathogenic role. The gene expression of IL-17A and IFN-γ were found to be significantly positively correlated with the percentage of CCR6⁺ ILCs. On the other hand, CCR6^neg ILCs were negatively correlated with ILC1 and ILC3 associated markers. Summarily our results clearly suggest that both ILC1 and ILC3 are important and immune-protective, on the contrary DP (IFN-γ⁺IL-17A⁺) ILCs may promote progression and immunopathology of leprosy.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"275 ","pages":"Article 107012"},"PeriodicalIF":3.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}