Nur77 controls tolerance induction, terminal differentiation, and effector functions in semi-invariant natural killer T cells.

ABSTRACT: Semi-invariant natural killer T (iNKT) cells are self-reactive lymphocytes, yet how this lineage attains self-tolerance remains unknown. iNKT cells constitutively express high levels of Nr4a1-encoded Nur77, a transcription factor that integrates signal strength downstream of the T cell receptor (TCR) within activated thymocytes and peripheral T cells. The function of Nur77 in iNKT cells is unknown. Here we report that sustained Nur77 overexpression (Nur77^tg) in mouse thymocytes abrogates iNKT cell development. Introgression of a rearranged Vα14-Jα18 TCR-α chain gene into the Nur77^tg (Nur77^tg;Vα14^tg) mouse rescued iNKT cell development up to the early precursor stage, stage 0. iNKT cells in bone marrow chimeras that reconstituted thy

SUBMITTER: Kumar A 

PROVIDER: S-EPMC7382224 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature