实验性自身免疫性脑脊髓炎
自身免疫
生物
免疫系统
T细胞
免疫学
分子生物学
作者
Irshad Akbar,Rui Tang,Joanie Baillargeon,Andrée-Pascale Roy,Prenitha Mercy Ignatius Arokia Doss,Chen Zhu,Vijay K. Kuchroo,Manu Rangachari
出处
期刊:Journal of Immunology
[The American Association of Immunologists]
日期:2023-11-01
卷期号:211 (12): 1762-1766
被引量:2
标识
DOI:10.4049/jimmunol.2300526
摘要
Abstract Th1 cells are critical in experimental autoimmune encephalomyelitis (EAE). Serine protease inhibitor clade E1 (Serpine1) has been posited as an inhibitor of IFN-γ from T cells, although its role in autoimmunity remains unclear. In this study, we show that Serpine1 knockout (KO) mice develop EAE of enhanced severity relative to wild-type (WT) controls. Serpine1 overexpression represses Th1 cell cytokine production and pathogenicity, whereas Serpine1-KO:2D2 Th1 cells transfer EAE of increased severity in comparison with WT 2D2 Th1 cells. Notably, polarized Serpine1-KO Th1 cells display delayed expression of the Th1-specific inhibitory receptor, Tim-3 (T cell Ig and mucin–domain containing-3). Serpine1-KO:Tim-3-Tg Th1 cells, which transgenically overexpress Tim-3, showed increased expression of IFN-γ and reduced expression of the checkpoint molecules Lag-3 and PD-1 relative to WT Tim-3-Tg counterparts. Furthermore, Serpine1 deficiency restored the EAE phenotype of Tim-3-Tg mice that normally develop mild disease. Taken together, we identify Serpine1 as a negative regulator of Th1 cells.
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