CCL20-CCR6 signaling alters the metabolic reprogramming to promote the pathogenic Th17 cell differentiation.

ABSTRACT: CCR6 is a G-protein-coupled receptor that binds to its ligand CCL20. Th17 and Foxp3⁺CD4⁺ T cells express CCR6, enabling their migration to inflamed tissues with unique metabolic environments. The factors that regulate their metabolic adaptation and functional roles in these tissues remain unclear. Using inflammatory bowel disease patient samples and experimental colitis models in mice, we demonstrated that the intrinsic signaling of CCL20-CCR6 in CD4⁺ T cells promotes the differentiation of inflammatory Th1-like Th17 cells (T-bet⁺RORγt⁺) during colitis. This signaling induces the rapamycin-sensitive phosphorylation of PI3K, Akt, mTORC1, and STAT3 in a CCR6-dependent manner. RNA-seq and proteomics analysis revealed that the addition of

SUBMITTER: Meitei HT 

PROVIDER: S-EPMC12794437 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature