多发性硬化
自身免疫
CD8型
生物
T细胞
免疫学
受体
刺激
封锁
免疫系统
内科学
内分泌学
医学
作者
Britta E. Jones,Megan D. Maerz,Henry T. Bahnson,Ashwin Somasundaram,Lucas McCarthy,Cate Speake,Jane H. Buckner
出处
期刊:Journal of Immunology
[The American Association of Immunologists]
日期:2022-02-01
卷期号:208 (3): 594-602
被引量:19
标识
DOI:10.4049/jimmunol.2100850
摘要
Abstract The coinhibitory receptor lymphocyte activation gene 3 (LAG-3) is an immune checkpoint molecule that negatively regulates T cell activation, proliferation, and homeostasis. Blockade or deletion of LAG-3 in autoimmune-prone backgrounds or induced-disease models has been shown to exacerbate disease. We observed significantly fewer LAG-3+ CD4 and CD8 T cells from subjects with relapsing-remitting multiple sclerosis (RRMS) and type 1 diabetes. Low LAG-3 protein expression was linked to alterations in mRNA expression and not cell surface cleavage. Functional studies inhibiting LAG-3 suggest that in subjects with RRMS, LAG-3 retains its ability to suppress T cell proliferation. However, LAG-3 expression was associated with the expression of markers of apoptosis, indicating a role for low LAG-3 in T cell resistance to cell death. In T cells from subjects with RRMS, we observed a global dysregulation of LAG-3 expression stemming from decreased transcription and persisting after T cell stimulation. These findings further support the potential clinical benefits of a LAG-3 agonist in the treatment of human autoimmunity.
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