Immunology letters最新文献

筛选
英文 中文
Unveiling the hidden syndrome: The enigma of anti-transcobalamin receptor autoantibodies 揭开隐藏的综合症:抗转钴胺素受体自身抗体之谜
IF 3.3 4区 医学
Immunology letters Pub Date : 2025-04-23 DOI: 10.1016/j.imlet.2025.107028
Kazuki M. Matsuda, Hirohito Kotani, Shinichi Sato, Ayumi Yoshizaki
{"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":"2025-04-23","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}
引用次数: 0
NETs activate AIM2 to mediate synovial fibroblast pyroptosis and promote acute gouty arthritis development net激活AIM2介导滑膜成纤维细胞焦亡,促进急性痛风性关节炎的发展
IF 3.3 4区 医学
Immunology letters Pub Date : 2025-04-22 DOI: 10.1016/j.imlet.2025.107007
Jing Tian , Ying Liu , Wei Gao , Xiuyun Shi , Feng Cheng , Bing Xie
{"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}
引用次数: 0
CD4+ T-cell help delivery to monocyte-derived dendritic cells promotes effector differentiation of helper and cytotoxic T cells CD4+ T 细胞对单核细胞衍生树突状细胞的帮助传递可促进辅助性和细胞毒性 T 细胞的效应分化
IF 3.3 4区 医学
Immunology letters Pub Date : 2025-04-14 DOI: 10.1016/j.imlet.2025.107022
Douwe M. T. Bosma , Julia Busselaar , Mo D. Staal , Elselien Frijlink , Matthias Mack , Fiamma Salerno , Jannie Borst
{"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<sup>+</sup> T-cell help optimizes CD8<sup>+</sup> T-cell effector and memory responses via CD40-mediated licensing of conventional dendritic cells (DCs). Using comparative vaccination settings that prime CD8<sup>+</sup> T cells in presence or absence of CD4<sup>+</sup> T-cell help, we observed that CD4<sup>+</sup> 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<sup>+</sup> T cells, as well as effector differentiation of CD8<sup>+</sup> T cells. Monocyte-derived cells in dLNs upregulated CD40, CD80 and PD-L1 as a result of CD4<sup>+</sup> T-cell help. The response of monocyte-derived cells to CD4<sup>+</sup> 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<sup>+</sup> T cells in dLNs crosstalk via CD40L and IFNγ signals to monocytes, promoting their local differentiation into MoDCs. This event enhances formation of CD4<sup>+</sup> Th1 and CD8<sup>+</sup> 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}
引用次数: 0
A novel MF59 and CpG1018 adjuvant combination enhances the humoral and cellular immune responses against a truncated varicella-zoster viral glycoprotein E 一种新的MF59和CpG1018佐剂组合增强了对截断水痘-带状疱疹病毒糖蛋白E的体液和细胞免疫反应
IF 3.3 4区 医学
Immunology letters Pub Date : 2025-04-14 DOI: 10.1016/j.imlet.2025.107025
Jing Yang , Xue Hu , Xiguang Chen , Wanzhen Li , Quanyi Yin , Yelin Xiong , Youcai An , Haiyan Li , Zhilei Liu
{"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}
引用次数: 0
Impact of afatinib on intestinal and salivary IgA: Immune response alterations linked to gastrointestinal side effects 阿法替尼对肠道和唾液IgA的影响:与胃肠道副作用相关的免疫反应改变
IF 3.3 4区 医学
Immunology letters Pub Date : 2025-04-12 DOI: 10.1016/j.imlet.2025.107024
Ippei Uemura, Natsuko Takahashi-Suzuki, Takashi Satoh
{"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}
引用次数: 0
Characteristics and specific differential gene analysis of the TCR immune repertoire in secondary adult HLH lymphocytes 成人继发性HLH淋巴细胞TCR免疫库特征及特异性差异基因分析
IF 3.3 4区 医学
Immunology letters Pub Date : 2025-04-12 DOI: 10.1016/j.imlet.2025.107023
Yongsheng Chen , Wenrui Xiao , Shiyi Yuan , Cong Wang , Meizhen Shi , Dan Yu , Ying Zhang , Shifeng Lou
{"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}
引用次数: 0
Inhibitor of differentiation-2 protein ameliorates complete Freund's adjuvant-induced arthritis and inhibits STAT3 phosphorylation in the synovium 分化-2蛋白抑制剂改善完全弗氏佐剂诱导的关节炎并抑制滑膜中STAT3磷酸化。
IF 3.3 4区 医学
Immunology letters Pub Date : 2025-04-05 DOI: 10.1016/j.imlet.2025.107008
Yang Haowen , Yao Yuhan , Liang Yuanyuan , Ma Xibin , Wang Yuxin , Xu Lingyun , Yan Dong , Li Min , Zhong Genshen , Wu Minna
{"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}
引用次数: 0
Remdesivir alleviates joint damage in collagen-induced arthritis and inhibits inflammatory cell death of RA synovial fibroblasts 瑞德西韦减轻胶原诱导关节炎的关节损伤,抑制RA滑膜成纤维细胞的炎症细胞死亡。
IF 3.3 4区 医学
Immunology letters Pub Date : 2025-04-05 DOI: 10.1016/j.imlet.2025.107009
A Ram Lee , Hong Ki Min , Seon-Yeong Lee , Su Been Jeon , Chae Rim Lee , Tae Ho Kim , Jin Hyung Park , Mi- La Cho
{"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}
引用次数: 0
The immune-reinforcements of Lenvatinib plus anti-PD-1 and their rationale to unite with TACE for unresectable hepatocellular carcinoma treatment Lenvatinib联合抗pd -1的免疫增强作用及其与TACE联合治疗不可切除肝细胞癌的原理
IF 3.3 4区 医学
Immunology letters Pub Date : 2025-04-04 DOI: 10.1016/j.imlet.2025.107003
Jiayun Jiang , Hui Zhang , Yanjiao Ou , Jiejuan Lai , Yulan Huang , Wenyun Cai , Chong Li , Leida Zhang , Yu Fu
{"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<sup>+</sup>, CD8<sup>+</sup> <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":"2025-04-04","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}
引用次数: 0
Double positive IL-17A+IFN-γ+CCR6+ ILCs contribute towards the immunopathology of lepromatous leprosy 双阳性IL-17A+IFN-γ+CCR6+ ilc参与麻风性麻风的免疫病理。
IF 3.3 4区 医学
Immunology letters Pub Date : 2025-04-04 DOI: 10.1016/j.imlet.2025.107012
Chaman Saini , Leena Sapra , V. Ramesh , Poonam Puri , Rupesh K. Srivastava
{"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<sup>neg</sup>CCR6<sup>+</sup>CD19<sup>neg</sup>IFN-γ<sup>+</sup> and CD3<sup>neg</sup>CCR6<sup>+</sup>CD19<sup>neg</sup>IL-17A<sup>+</sup>, respectively, by flow-cytometry analysis. BT skin lesions represents high CCR6<sup>+</sup>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<sup>neg</sup>CCR6<sup>+</sup>CD19<sup>neg</sup>IFN-γ<sup>+</sup>IL-17A<sup>+</sup> 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<sup>+</sup> ILCs. On the other hand, CCR6<sup>neg</sup> 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<sup>+</sup>IL-17A<sup>+</sup>) 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":"2025-04-04","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}
引用次数: 0
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
相关产品
×
本文献相关产品
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信