| First Author | Buzzelli AA | Year | 2023 |
| Journal | J Immunol | Volume | 210 |
| Issue | 11 | Pages | 1667-1676 |
| PubMed ID | 37093664 | Mgi Jnum | J:340106 |
| Mgi Id | MGI:7518439 | Doi | 10.4049/jimmunol.2200606 |
| Citation | Buzzelli AA, et al. (2023) Intrinsic STAT4 Expression Controls Effector CD4 T Cell Migration and Th17 Pathogenicity. J Immunol 210(11):1667-1676 |
| abstractText | 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. |
