CD305 participates in abnormal activation of memory CD4+ T cells in patients with RA and attenuates collagen-induced arthritis

IF 3.2 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Molecular immunology Pub Date : 2024-07-29 DOI:10.1016/j.molimm.2024.07.010
Minghua Lyu , Pengtao Jiang , Bin Li , Zhifang Hu , Na Guo
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Abstract

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that mainly affects the joints. Studies have shown that memory CD4+ T cells play an important role in the pathogenesis of RA. This study investigated the expression and function of CD305 on human memory CD4+ T cells and the effects of CD305 activating antibody on collagen-induced arthritis. The results showed that CD305 expression was significantly decreased on circulating memory CD4+ T cells from patients with RA and its mean fluorescence intensity (MFI) was negatively correlated with DAS28. Moreover, CD305 inhibited the activation of memory CD4+ T cells by down-regulating CD69 and CD25 and the production of IFN-γ, IL-4, and IL-17A induced by anti-CD3/CD28 antibodies. In addition, activation of CD305 inhibited the severity of disease in collagen-induced arthritis. In summary, CD305 reduction may mediate the excessive activation of memory CD4+ T cells and participate in the development of RA. It can be used as a predictive marker of disease activity and has potential medicinal value in the treatment of RA.

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CD305 参与了 RA 患者记忆 CD4+ T 细胞的异常激活,并减轻了胶原蛋白诱导的关节炎。
类风湿性关节炎(RA)是一种主要影响关节的慢性全身性自身免疫性疾病。研究表明,记忆 CD4+ T 细胞在 RA 的发病机制中起着重要作用。本研究探讨了 CD305 在人类记忆 CD4+ T 细胞上的表达和功能,以及 CD305 激活抗体对胶原诱导的关节炎的影响。结果显示,CD305在RA患者循环记忆CD4+ T细胞上的表达明显下降,其平均荧光强度(MFI)与DAS28呈负相关。此外,CD305通过下调CD69和CD25以及抗CD3/CD28抗体诱导的IFN-γ、IL-4和IL-17A的产生,抑制了记忆CD4+ T细胞的活化。此外,激活 CD305 还能抑制胶原诱导的关节炎的病情严重程度。总之,CD305 的减少可能会介导记忆 CD4+ T 细胞的过度活化,并参与 RA 的发病。它可作为疾病活动性的预测标志物,在治疗 RA 方面具有潜在的药用价值。
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来源期刊
Molecular immunology
Molecular immunology 医学-免疫学
CiteScore
6.90
自引率
2.80%
发文量
324
审稿时长
50 days
期刊介绍: Molecular Immunology publishes original articles, reviews and commentaries on all areas of immunology, with a particular focus on description of cellular, biochemical or genetic mechanisms underlying immunological phenomena. Studies on all model organisms, from invertebrates to humans, are suitable. Examples include, but are not restricted to: Infection, autoimmunity, transplantation, immunodeficiencies, inflammation and tumor immunology Mechanisms of induction, regulation and termination of innate and adaptive immunity Intercellular communication, cooperation and regulation Intracellular mechanisms of immunity (endocytosis, protein trafficking, pathogen recognition, antigen presentation, etc) Mechanisms of action of the cells and molecules of the immune system Structural analysis Development of the immune system Comparative immunology and evolution of the immune system "Omics" studies and bioinformatics Vaccines, biotechnology and therapeutic manipulation of the immune system (therapeutic antibodies, cytokines, cellular therapies, etc) Technical developments.
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