Cancer-associated SF3B1-K700E mutation controls immune responses by regulating T_reg function via aberrant Anapc13 splicing.

ABSTRACT: Recurrent somatic mutations in spliceosome factor 3b subunit 1 (SF3B1) are identified in hematopoietic malignancies, with SF3B1-K700E being the most common one. Here, we show that regulatory T cell (T_reg)-specific expression of SF3B1-K700E (Sf3b1^K700Efl/+/Foxp3^YFP-Cre) results in spontaneous autoimmune phenotypes. CD4⁺ T cells from Sf3b1^K700Efl/+/Foxp3^YFP-Cre mice display defective T_reg differentiation and inhibitory function, which is demonstrated by failed prevention of adoptive transfer colitis by Sf3b1^K700Efl/+/Foxp3^YFP-Cre T_regs. Mechanically, SF3B1-K700E induces an aberrant splicing event that results in reduced expression of a cell proliferation regulato

SUBMITTER: Shi Y 

PROVIDER: S-EPMC11414738 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature