Aberrant pro-inflammatory responses of CD20+ T cells in experimental arthritis

IF 3.7 4区 医学 Q2 CELL BIOLOGY
Piaopiao Pan , Miguel A. Pineda , Yilin Wang , Aneesah Khan , Mukanthu H. Nyirenda
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Abstract

CD20+ T cells comprise a highly inflammatory subset implicated in autoimmunity, including rheumatoid arthritis (RA). We sought to characterize the CD20+ T cell subset in the murine collagen-induced arthritis (CIA) model of RA and investigate the phenotype and functional relevance of CD3+CD20+ T cells in the lymph nodes and arthritic joints using flow cytometry and immunohistochemistry. We demonstrate that CD3+CD4+CD20+ and CD3+CD8+CD20+ T cells are expanded in the draining lymph nodes of CIA mice, produce increased levels of pro-inflammatory cytokines and are less susceptible to regulation by regulatory T cells. Notably, CD3+CD4+CD20+ and CD3+CD8+CD20+ T cells are enriched with CXCR5+PD-1+ T follicular helper cells and CXCR5-PD-1+ peripheral T helper cells, subsets of T cells implicated in promoting B-cell responses and antibody production within pathologically inflamed non-lymphoid tissues in RA. Our findings suggest CD20+ T cells are associated with inflammatory responses and may exacerbate pathology by promoting inflammatory B-cell responses.

Abstract Image

CD20+T细胞在实验性关节炎中的异常促炎反应
CD20+T细胞包含与自身免疫有关的高度炎症亚群,包括类风湿性关节炎(RA)。我们试图在RA的小鼠胶原诱导性关节炎(CIA)模型中表征CD20+T细胞亚群,并使用流式细胞术和免疫组织化学研究淋巴结和关节炎关节中CD3+CD20+T细胞的表型和功能相关性。我们证明CD3+CD4+CD20+和CD3+CD8+CD20+T细胞在CIA小鼠的引流淋巴结中扩增,产生水平增加的促炎细胞因子,并且对调节性T细胞的调节不太敏感。值得注意的是,CD3+CD4+CD20+和CD3+CD8+CD20+T细胞富含CXCR5+PD-1+T滤泡辅助细胞和CXCR5-PD-1+外周T辅助细胞,这些T细胞亚群参与促进RA病理炎症非淋巴组织中的B细胞反应和抗体产生。我们的研究结果表明,CD20+T细胞与炎症反应有关,并可能通过促进炎症B细胞反应而加剧病理。
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来源期刊
Cellular immunology
Cellular immunology 生物-免疫学
CiteScore
8.20
自引率
2.30%
发文量
102
审稿时长
30 days
期刊介绍: Cellular Immunology publishes original investigations concerned with the immunological activities of cells in experimental or clinical situations. The scope of the journal encompasses the broad area of in vitro and in vivo studies of cellular immune responses. Purely clinical descriptive studies are not considered. Research Areas include: • Antigen receptor sites • Autoimmunity • Delayed-type hypersensitivity or cellular immunity • Immunologic deficiency states and their reconstitution • Immunologic surveillance and tumor immunity • Immunomodulation • Immunotherapy • Lymphokines and cytokines • Nonantibody immunity • Parasite immunology • Resistance to intracellular microbial and viral infection • Thymus and lymphocyte immunobiology • Transplantation immunology • Tumor immunity.
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