SerpinB1 controls encephalitogenic T helper cells in neuroinflammation

Lifei Hou, Deepak A. Rao, Koichi Yuki, Jessica Cooley, Lauren A. Henderson, A. Helena Jonsson, Dion Kaiserman, Mark P. Gorman, Peter A. Nigrovic, Phillip I. Bird, Burkhard Becher, Eileen Remold-O’Donnell

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25 Citations (Scopus)


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, 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+ 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.

Original languageEnglish
Pages (from-to)20635-20643
Number of pages9
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number41
Publication statusPublished - 8 Oct 2019


  • Autoimmune
  • Inflammatory arthritis
  • Multiple sclerosis
  • Pathogenic T helper cells
  • Serpins

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