Header

UZH-Logo

Maintenance Infos

SerpinB1 controls encephalitogenic T helper cells in neuroinflammation


Hou, Lifei; Rao, Deepak A; Yuki, Koichi; Cooley, Jessica; Henderson, Lauren A; Jonsson, A Helena; Kaiserman, Dion; Gorman, Mark P; Nigrovic, Peter A; Bird, Phillip I; Becher, Burkhard; Remold-O'Donnell, Eileen (2019). SerpinB1 controls encephalitogenic T helper cells in neuroinflammation. Proceedings of the National Academy of Sciences of the United States of America, 116(41):20635-20643.

Abstract

SerpinB1, a protease inhibitor and neutrophil survival factor, was recently linked with IL-17-expressing T cells. Here, we show that () is dramatically induced in a subset of effector CD4 cells in experimental autoimmune encephalomyelitis (EAE). Despite normal T cell priming, mice are resistant to EAE with a paucity of T helper (T) 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 mice, CXCR6 T 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 deletion, dramatically reverts EAE, strongly indicating that the CXCR6 T cells are the drivers of encephalitis.

Abstract

SerpinB1, a protease inhibitor and neutrophil survival factor, was recently linked with IL-17-expressing T cells. Here, we show that () is dramatically induced in a subset of effector CD4 cells in experimental autoimmune encephalomyelitis (EAE). Despite normal T cell priming, mice are resistant to EAE with a paucity of T helper (T) 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 mice, CXCR6 T 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 deletion, dramatically reverts EAE, strongly indicating that the CXCR6 T cells are the drivers of encephalitis.

Statistics

Citations

Dimensions.ai Metrics

Altmetrics

Downloads

0 downloads since deposited on 15 Nov 2019
0 downloads since 12 months

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Experimental Immunology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Scopus Subject Areas:Health Sciences > Multidisciplinary
Language:English
Date:8 October 2019
Deposited On:15 Nov 2019 10:22
Last Modified:29 Jul 2020 11:46
Publisher:National Academy of Sciences
ISSN:0027-8424
OA Status:Closed
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1073/pnas.1905762116
PubMed ID:31548399

Download

Closed Access: Download allowed only for UZH members