Intrinsic STAT4 Expression Controls Effector CD4 T Cell Migration and Th17 Pathogenicity.

Ashlyn A Buzzelli, Ian L McWilliams, Boyoung Shin, Morgan T Bryars, Laurie E Harrington

Journal of immunology (Baltimore, Md. : 1950) 2023 Jun 01

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Effector CD4 T cells are central to the development of autoimmune chronic inflammatory diseases, yet factors that mediate pathogenicity remain ill-defined. Single-nucleotide polymorphisms in the human STAT4 locus are associated with susceptibility to multiple autoimmune disorders, and Stat4 is linked to the pathogenic Th17 gene signature; however, Th17 cells differentiate independently of STAT4. Hence the interplay between STAT4 and CD4 T cell function, especially Th17 cells, during autoimmune disease is unclear. In this article, we demonstrate that CD4 T cell-intrinsic STAT4 expression is essential for the induction of autoimmune CNS inflammation in mice, in part by regulating the migration of CD4 T cells to the inflamed CNS. Moreover, unbiased transcriptional profiling revealed that STAT4 controls the expression of >200 genes in Th17 cells and is important for the upregulation of genes associated with IL-23-stimulated, pathogenic Th17 cells. Importantly, we show that Th17 cells specifically require STAT4 to evoke autoimmune inflammation, highlighting, to our knowledge, a novel function for STAT4 in Th17 pathogenicity. Copyright © 2023 by The American Association of Immunologists, Inc.

Citation

Ashlyn A Buzzelli, Ian L McWilliams, Boyoung Shin, Morgan T Bryars, Laurie E Harrington. Intrinsic STAT4 Expression Controls Effector CD4 T Cell Migration and Th17 Pathogenicity. Journal of immunology (Baltimore, Md. : 1950). 2023 Jun 01;210(11):1667-1676