Combined deletion of Id2 and Id3 genes reveals multiple roles for E proteins in invariant NKT cell development and expansion.
Journal Article (Journal Article)
The invariant NKT (iNKT) cells represent a unique group of αβ T cells that have been classified based on their exclusive usage of the invariant Vα14Jα18 TCRα-chain and their innate-like effector function. Thus far, the transcriptional programs that control Vα14Jα18 TCRα 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 Vα14 to Jα18 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 γδ 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.
Full Text
Duke Authors
Cited Authors
- Li, J; Wu, D; Jiang, N; Zhuang, Y
Published Date
- November 15, 2013
Published In
Volume / Issue
- 191 / 10
Start / End Page
- 5052 - 5064
PubMed ID
- 24123680
Pubmed Central ID
- PMC3837387
Electronic International Standard Serial Number (EISSN)
- 1550-6606
Digital Object Identifier (DOI)
- 10.4049/jimmunol.1301252
Language
- eng
Conference Location
- United States