| First Author | Zhong X | Year | 2024 |
| Journal | Cell Rep | Volume | 43 |
| Issue | 11 | Pages | 114951 |
| PubMed ID | 39504243 | Mgi Jnum | J:360636 |
| Mgi Id | MGI:7790343 | Doi | 10.1016/j.celrep.2024.114951 |
| Citation | Zhong X, et al. (2024) Distinct RORgammat-dependent Th17 immune responses are required for autoimmune pathogenesis and protection against bacterial infection. Cell Rep 43(11):114951 |
| abstractText | T helper (Th)17 cells mediate both protective anti-bacterial immune responses and autoimmune pathogenesis, but the distinct pathways regulating these Th17 responses remain unclear. Retinoid-related orphan receptor gamma t (RORgammat) is a master transcription factor that governs Th17 cell generation and effector functions. We found that a K256R mutation in RORgammat impairs Th17-mediated experimental autoimmune encephalomyelitis (EAE) without affecting the clearance of Citrobacter rodentium. This indicates distinct RORgammat roles in central nervous system pathogenesis versus gut-associated protective Th17 responses. Mechanically, RORgammat/Runx1-dependent upregulation of galectin-3 (Lgals3) and chemokine receptor Ccr6 in CD4(+) T cells is essential for EAE development but not for bacterial clearance. Moreover, Lgals3 is selectively required for recruiting macrophages to produce interleukin (IL)-1beta, which in turn promotes Ccr6 expression on CD4(+) T cells during EAE pathogenesis. Our findings highlight different RORgammat-regulated Th17 pathways in autoimmunity and anti-bacterial immunity, with implications for therapies targeting Th17-mediated autoimmunity while preserving effective anti-bacterial responses. |
