Combined deletion of Id2 and Id3 genes reveals multiple roles for E proteins in invariant NKT cell development and expansion.

ABSTRACT: The invariant NKT (iNKT) cells represent a unique group of ?? T cells that have been classified based on their exclusive usage of the invariant V?14J?18 TCR?-chain and their innate-like effector function. Thus far, the transcriptional programs that control V?14J?18 TCR? rearrangements and the population size of iNKT cells are still incompletely defined. E protein transcription factors have been shown to play necessary roles in the development of multiple T cell lineages, including iNKT cells. In this study, we examined E protein functions in T cell development through combined deletion of genes encoding E protein inhibitors Id2 and Id3. Deletion of Id2 and Id3 in T cell progenitors resulted in a partial block at the pre-TCR selection checkpoint and a dramatic increase in numbers of iNKT cells. The increase in iNKT cells is accompanied with a biased rearrangement involving V?14 to J?18 recombination at the double-positive stage and enhanced proliferation of iNKT cells. We further demonstrate that a 50% reduction of E proteins can cause a dramatic switch from iNKT to innate-like ?? T cell fate in Id2- and Id3-deficient mice. Collectively, these findings suggest that Id2- and Id3-mediated inhibition of E proteins controls iNKT development by restricting lineage choice and population expansion.

SUBMITTER: Li J 

PROVIDER: S-EPMC3837387 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature