Intergenic risk variant rs56258221 skews the fate of naive CD4⁺ T cells via miR4464-BACH2 interplay in primary sclerosing cholangitis.

ABSTRACT: Primary sclerosing cholangitis (PSC) is an immune-mediated liver disease of unknown pathogenesis, with a high risk to develop cirrhosis and malignancies. Functional dysregulation of T cells and association with genetic polymorphisms in T cell-related genes were previously reported for PSC. Here, we genotyped a representative PSC cohort for several disease-associated risk loci and identified rs56258221 (BACH2/MIR4464) to correlate with not only the peripheral blood T cell immunophenotype but also the functional capacities of naive CD4⁺ T (CD4⁺ T_N) cells in people with PSC. Mechanistically, rs56258221 leads to an increased expression of miR4464, in turn causing attenuated translation of BACH2, a major gatekeeper of T cell quiescence. Thereby, the fate of CD4<

SUBMITTER: Poch T 

PROVIDER: S-EPMC11293351 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature