Immunology letters最新文献

{"title":"Identification of S100A9 as a target for diagnosis and treatment of Crohn’s Disease after Vedolizumab treatment failure","authors":"Yanru Zhang ,&nbsp;Zhe Zhang ,&nbsp;Ruixian Liu,&nbsp;Yijia He,&nbsp;Shiyang Ning,&nbsp;Junzhi Yu,&nbsp;Yan Liu,&nbsp;Yimeng Xia,&nbsp;Xinji Pang,&nbsp;Wen Lv,&nbsp;Qiankun Sun,&nbsp;Yilong Li,&nbsp;Zhihong Wang,&nbsp;Lu Liu,&nbsp;Baisui Feng","doi":"10.1016/j.imlet.2025.107027","DOIUrl":"10.1016/j.imlet.2025.107027","url":null,"abstract":"<div><div>The vedolizumab medication is the treatment that precisely targets the gut for Crohn’s Disease (CD). It can inhibit the migration of lymphocytes to the intestinal site despite the fact that a significant portion of the population continues to be ineffectively treated. In this study, peripheral blood leukocytes sampled from the CD patients who are nonresponsive or responsive to vedolizumab treatment were used for transcriptome sequencing. Intersected differentially expressed mRNA obtained from transcriptome sequencing and GSE191328 were utilized to predict key therapeutic targets. Bioinformatics analyses were used to explore potential biological mechanisms and to screen pivotal genes. Inhibitor of S100A9 increased the body weight and colon length of mice with colitis, and decreased the DAI score. Our study also demonstrated that the combination of anti-α4β7 integrin antibody with inhibitor of S100A9 further alleviates colitis. Through flow cytometry, changes in the composition of immune cell populations in colon tissues were found after intragastric administration of paquinimod, an inhibitor of S100A9. It is important that blocking S100A9 inhibited the recruitment of neutrophils in the mice’s colon. Our findings lay a foundation for the further exploration of the new targets for non-responders to vedolizumab in CD patients.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"275 ","pages":"Article 107027"},"PeriodicalIF":3.3,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143941709","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":"NETs activate AIM2 to mediate synovial fibroblast pyroptosis and promote acute gouty arthritis development","authors":"Jing Tian ,&nbsp;Ying Liu ,&nbsp;Wei Gao ,&nbsp;Xiuyun Shi ,&nbsp;Feng Cheng ,&nbsp;Bing Xie","doi":"10.1016/j.imlet.2025.107007","DOIUrl":"10.1016/j.imlet.2025.107007","url":null,"abstract":"<div><h3>Background</h3><div>Acute gouty arthritis is a metabolic disease characterized by hyperuricemia, with acute attacks involving neutrophil-released NETs activating immune responses through their major component, DNA, as danger-associated molecular patterns (DAMPs).</div></div><div><h3>Objective</h3><div>To investigate whether DNA from NETs activates the AIM2 inflammasome in synovial fibroblasts during acute gouty arthritis attacks, inducing pyroptosis and exacerbating inflammation.</div></div><div><h3>Methods</h3><div>The AIM2 gene knockdown mouse model of acute gouty arthritis was constructed, the joint pathological changes were observed by H&amp;E staining, the synovium fibroblasts and neutrophils were sorted by flow cytometry, and the expressions of AIM2, Caspase-1 and GSDMD related proteins were detected by Western blot. The levels of TNF-α, IL-6, IL-1β and IL-18 in serum and cell supernatant were detected by ELISA. Neutrophils were induced to release NETs by urate, and NETs markers (dsDNA, MPO-DNA, NE-DNA) were detected by immunofluorescence (Cit-H3, PAD4) and ELISA. NETs media were co-cultured with synovial fibroblasts, cell activity and migration were evaluated by CCK8 and scrape assay, markers of synovitis (Thy1, VCAM-1, PDPN) were detected by immunofluorescence, and pyroptosis was evaluated by TUNEL and LDH release. By silencing or overexpression of AIM2 gene, Western blot and ELISA, the role of AIM2 in NETs induced pyrodeath and inflammatory response was investigated.</div></div><div><h3>Results</h3><div>AIM2 gene knockdown significantly alleviated the symptoms of MSU-induced acute gouty arthritis in mice, reducing joint swelling and pathological damage. Expression levels of inflammatory factors (TNF-α, IL-6, IL-1β, IL-18) and cleaved Caspase-1/Caspase-1, GSDMD-NT/GSDMD) were decreased. It was found that neutrophils released NETs in response to sodium urate stimulation, manifested by significant upregulation of Cit-H3 and PAD4, as well as increased dsDNA, MPO-DNA, and NE-DNA complexes. NETs can induce inflammatory response in synovial fibroblasts, which is manifested as decreased cell activity and migration ability, increased release of inflammatory factors, and significantly increased markers of synovitis (Thy1, VCAM-1, PDPN). In addition, NETs induce scorch death of synovium fibroblasts by activating AIM2 inflammatories, which aggravates the inflammatory response, and AIM2 gene knockdown can effectively inhibit the scorch death and inflammatory response induced by NETs, indicating that NETs play a key role in the occurrence and development of gout arthritis through AIM2-mediated scorch death of synovium fibroblasts.</div></div><div><h3>Conclusion</h3><div>NETs-activated AIM2-mediated synovial fibroblast pyroptosis plays a crucial role in acute gouty arthritis, providing a new therapeutic target.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"275 ","pages":"Article 107007"},"PeriodicalIF":3.3,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143855872","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":"Mast cell activation signature as a potential biomarker in COVID-19","authors":"Yatsiri G. Meneses-Preza ,&nbsp;Rodolfo Soria-Castro ,&nbsp;Ángel R. Alfaro-Doblado ,&nbsp;Alejandro Hernández-Solis ,&nbsp;Pablo Álvarez-Maldonado ,&nbsp;Diana Gómez-Martín ,&nbsp;Jiram Torres-Ruiz ,&nbsp;José Francisco Muñoz-Valle ,&nbsp;Guillermina Muñoz-Ríos ,&nbsp;Cristian Oswaldo Hernández-Ramírez ,&nbsp;Azmavet M. Güemes-González ,&nbsp;Isabel Wong-Baeza ,&nbsp;José Luis Maravillas-Montero ,&nbsp;Sonia M. Pérez-Tapia ,&nbsp;Alma D. Chávez-Blanco ,&nbsp;Sergio Estrada-Parra ,&nbsp;Rommel Chacón-Salinas","doi":"10.1016/j.imlet.2025.107026","DOIUrl":"10.1016/j.imlet.2025.107026","url":null,"abstract":"<div><div>The COVID-19 pandemic, caused by the SARS-CoV-2 virus, represented a public health challenge due to the absence of effective treatments to combat the disease. Lethality associated with SARS-CoV-2 infection results from an exacerbated immune response that mediates clinical disease progression and compromises respiratory capacity and organ function. In the lungs, one of the cell lineages increased during COVID-19 are mast cells (MC), cells of innate immune response known for their ability to promote inflammation through the release of their pre-formed mediators or <em>de novo</em> synthesis. The role of MC-derived mediators during SARS-CoV-2 infection and their association with the development of severe COVID-19 have been poorly described. In a previous report, we demonstrated the predictive ability of carboxypeptidase A3 (CPA3) to determine COVID-19 severity. However, it is currently unclear whether the use of other mast cell-derived mediators could improve this predictive ability. To address this gap, we evaluated levels of total tryptase, CPA3, chymase, and prostaglandin D2 (PGD2) in serum from patients with non-severe and severe COVID-19 to develop a predictive model of severe COVID-19 outcomes. We demonstrate that the combined use of these mediators enhances their predictive ability for MC activation during SARS-CoV-2 infection and their involvement in severe forms of COVID-19. Based on these findings, a serum MC activation profile can be proposed as a promising biomarker for SARS-CoV-2 infection and may contribute to the development of targeted therapeutic strategies to improve patient outcomes.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"275 ","pages":"Article 107026"},"PeriodicalIF":3.3,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143885558","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":"2025-04-14","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":"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":"2025-04-14","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":"Impact of afatinib on intestinal and salivary IgA: Immune response alterations linked to gastrointestinal side effects","authors":"Ippei Uemura,&nbsp;Natsuko Takahashi-Suzuki,&nbsp;Takashi Satoh","doi":"10.1016/j.imlet.2025.107024","DOIUrl":"10.1016/j.imlet.2025.107024","url":null,"abstract":"<div><h3>Background</h3><div>Afatinib, an oral molecular-targeted anticancer agent, is effective but causes significant gastrointestinal side effects. These effects are associated with EGFR inhibition in intestinal cells and changes in the microbiota.</div></div><div><h3>Objective</h3><div>To investigate the effects of afatinib on intestinal mucosal immunity in rats, focusing on IgA levels in the intestine and saliva, and to understand the innate and acquired immune responses to these side effects.</div></div><div><h3>Methods</h3><div>Male Wistar rats received afatinib (5.2 mg/kg) daily for 24 h (Day 1) and for 2 weeks (Day 14). Gene expression in the intestine was analyzed using quantitative polymerase chain reaction. IgA levels in the intestine and saliva were measured using enzyme-linked immunosorbent assay.</div></div><div><h3>Results</h3><div>Afatinib suppressed α-defensin 5 and pIgR in the jejunum and ileum, indicating reduced innate immunity. It increased IgA levels in the intestine and saliva, suggesting altered acquired immunity. Salivary IgA levels significantly correlated with intestinal IgA levels.</div></div><div><h3>Conclusions</h3><div>Afatinib affects gastrointestinal mucosal immunity, suppresses innate defense, and alters IgA production. Salivary IgA could serve as a marker for monitoring these effects, aiding cancer therapy management.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"275 ","pages":"Article 107024"},"PeriodicalIF":3.3,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143843090","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":"2025-04-12","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":"Corrigendum to “The role of IgA in gastrointestinal helminthiasis: A systematic review” [Immunology Letters (2022) 12-22, Volume: 249]","authors":"Anne C.S. Ramos ,&nbsp;Luciana M. Oliveira ,&nbsp;Yvanna L.D.C.O. Santos ,&nbsp;Marlon C.S. Dantas ,&nbsp;Cristiani I.B. Walker ,&nbsp;Ana M.C. Faria ,&nbsp;Lílian L. Bueno ,&nbsp;Silvio S. Dolabella ,&nbsp;Ricardo T. Fujiwara","doi":"10.1016/j.imlet.2025.107011","DOIUrl":"10.1016/j.imlet.2025.107011","url":null,"abstract":"","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"275 ","pages":"Article 107011"},"PeriodicalIF":3.3,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143978094","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":"Inhibitor of differentiation-2 protein ameliorates complete Freund's adjuvant-induced arthritis and inhibits STAT3 phosphorylation in the synovium","authors":"Yang Haowen ,&nbsp;Yao Yuhan ,&nbsp;Liang Yuanyuan ,&nbsp;Ma Xibin ,&nbsp;Wang Yuxin ,&nbsp;Xu Lingyun ,&nbsp;Yan Dong ,&nbsp;Li Min ,&nbsp;Zhong Genshen ,&nbsp;Wu Minna","doi":"10.1016/j.imlet.2025.107008","DOIUrl":"10.1016/j.imlet.2025.107008","url":null,"abstract":"<div><div>Rheumatoid arthritis (RA) is a chronic autoimmune disease causing joint inflammation, dysfunction, and deformity, along with systemic inflammatory manifestations. Inhibitor of differentiation-2 (ID2) is a transcription factor containing a helix-loop-helix (HLH) structure. Studies suggest that ID2 regulates innate and adaptive immunity and inhibits the differentiation of osteoclasts. However, the effects and underlying molecular mechanisms of ID2 on rheumatoid arthritis (RA) remain unclear. In the present study, we found that exogenous supplementation of human recombinant ID2 (hID2) protein significantly reduced paw swelling and arthritis index scores in adjuvant-induced arthritis (AIA) rats, and improved ankle joint pathology. Analysis of pro-inflammatory factor levels in peripheral blood mononuclear cells and synovial tissues indicated that hID2 attenuated inflammatory responses in AIA rats. Furthermore, RNA sequencing demonstrated that hID2 down-regulated the JAK-STAT pathway, and the phosphorylation of its key molecule, Signal Transducer and Activator of Transcription 3 (STAT3), was inhibited in synovial tissues. Additionally, the expression of chemokine-related genes was noticeably down-regulated in synovial tissues, though further investigation is needed to understand the underlying mechanisms. Overall, these findings suggest that hID2 effectively attenuated the inflammatory response and joint destruction in AIA rats, highlighting the potential of hID2 as a therapeutic agent for the treatment of RA.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"275 ","pages":"Article 107008"},"PeriodicalIF":3.3,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803128","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":"2025-04-05","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}