Positive regulation of Vav1 by Themis controls CD4 T cell pathogenicity in a mouse model of central nervous system inflammation.

ABSTRACT: The susceptibility to autoimmune diseases is conditioned by the association of modest genetic alterations which altogether weaken self-tolerance. The mechanism whereby these genetic interactions modulate T-cell pathogenicity remains largely uncovered. Here, we investigated the epistatic interaction of two interacting proteins involved in T Cell Receptor signaling and which were previously associated with the development of Multiple Sclerosis. To this aim, we used mice expressing an hypomorphic variant of Vav1 (Vav1^R63W), combined with a T cell-conditional deletion of Themis. We show that the combined mutations in Vav1 and Themis induce a strong attenuation of the severity of Experimental Autoimmune Encephalomyelitis (EAE), contrasting with the moderate effect of the single mutat

SUBMITTER: Marrocco R 

PROVIDER: S-EPMC10987373 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature