期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2019
卷号：116
期号：41
页码：20635-20643
DOI：10.1073/pnas.1905762116
出版社：The National Academy of Sciences of the United States of America
摘要：SerpinB1, a protease inhibitor and neutrophil survival factor, was recently linked with IL-17–expressing T cells. Here, we show that serpinB1 ( Sb1 ) is dramatically induced in a subset of effector CD4 cells in experimental autoimmune encephalomyelitis (EAE). Despite normal T cell priming, Sb1 −/− mice are resistant to EAE with a paucity of T helper (T H ) cells that produce two or more of the cytokines, IFNγ, GM-CSF, and IL-17. These multiple cytokine-producing CD4 cells proliferate extremely rapidly; highly express the cytolytic granule proteins perforin-A, granzyme C (GzmC), and GzmA and surface receptors IL-23R, IL-7Rα, and IL-1R1; and can be identified by the surface marker CXCR6. In Sb1 −/− mice, CXCR6 + T H cells are generated but fail to expand due to enhanced granule protease-mediated mitochondrial damage leading to suicidal cell death. Finally, anti-CXCR6 antibody treatment, like Sb1 deletion, dramatically reverts EAE, strongly indicating that the CXCR6 + T cells are the drivers of encephalitis..
