| First Author | Hou L | Year | 2019 |
| Journal | Proc Natl Acad Sci U S A | Volume | 116 |
| Issue | 41 | Pages | 20635-20643 |
| PubMed ID | 31548399 | Mgi Jnum | J:280501 |
| Mgi Id | MGI:6367504 | Doi | 10.1073/pnas.1905762116 |
| Citation | Hou L, et al. (2019) SerpinB1 controls encephalitogenic T helper cells in neuroinflammation. Proc Natl Acad Sci U S A 116(41):20635-20643 |
| abstractText | 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 (TH) cells that produce two or more of the cytokines, IFNgamma, 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-7Ralpha, and IL-1R1; and can be identified by the surface marker CXCR6. In Sb1 (-/-) mice, CXCR6(+) TH 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. |
