Targeting abatacept-resistant T-helper-17 cells by aldehyde dehydrogenase inhibition.

ABSTRACT: IL-17-producing helper T (Th17) cells are long-lived and serve as central effector cells in chronic autoimmune diseases. The underlying mechanisms of Th17 persistence remain unclear. We demonstrated that abatacept, a CD28 antagonist, effectively prevented the development of skin disease in a Th17-dependent experimental autoimmune dermatitis model. Abatacept selectively inhibited the emergence of IL-7R-negative effector-phenotype T cells while allowing the survival and proliferation of IL-7R⁺ memory-phenotype cells. The surviving IL-7R⁺ Th17 cells expressed genes associated with alcohol/aldehyde detoxification and showed potential to transdifferentiate into IL-7R-negative effector cells. Inhibiting aldehyde dehydrogenase reduced IL-7R⁺ Th17 cells in vivo<

SUBMITTER: Tokifuji Y 

PROVIDER: S-EPMC10788227 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature