| First Author | Wu B | Year | 2021 |
| Journal | Immunity | Volume | 54 |
| Issue | 2 | Pages | 308-323.e6 |
| PubMed ID | 33421362 | Mgi Jnum | J:305833 |
| Mgi Id | MGI:6706586 | Doi | 10.1016/j.immuni.2020.12.010 |
| Citation | Wu B, et al. (2021) The TGF-beta superfamily cytokine Activin-A is induced during autoimmune neuroinflammation and drives pathogenic Th17 cell differentiation. Immunity 54(2):308-323.e6 |
| abstractText | Th17 cells are known to exert pathogenic and non-pathogenic functions. Although the cytokine transforming growth factor beta1 (TGF-beta1) is instrumental for Th17 cell differentiation, it is dispensable for generation of pathogenic Th17 cells. Here, we examined the T cell-intrinsic role of Activin-A, a TGF-beta superfamily member closely related to TGF-beta1, in pathogenic Th17 cell differentiation. Activin-A expression was increased in individuals with relapsing-remitting multiple sclerosis and in mice with experimental autoimmune encephalomyelitis. Stimulation with interleukin-6 and Activin-A induced a molecular program that mirrored that of pathogenic Th17 cells and was inhibited by blocking Activin-A signaling. Genetic disruption of Activin-A and its receptor ALK4 in T cells impaired pathogenic Th17 cell differentiation in vitro and in vivo. Mechanistically, extracellular-signal-regulated kinase (ERK) phosphorylation, which was essential for pathogenic Th17 cell differentiation, was suppressed by TGF-beta1-ALK5 but not Activin-A-ALK4 signaling. Thus, Activin-A drives pathogenic Th17 cell differentiation, implicating the Activin-A-ALK4-ERK axis as a therapeutic target for Th17 cell-related diseases. |
