| First Author | Li J | Year | 2013 |
| Journal | J Immunol | Volume | 191 |
| Issue | 10 | Pages | 5052-64 |
| PubMed ID | 24123680 | Mgi Jnum | J:206330 |
| Mgi Id | MGI:5550032 | Doi | 10.4049/jimmunol.1301252 |
| Citation | Li J, et al. (2013) Combined deletion of Id2 and Id3 genes reveals multiple roles for E proteins in invariant NKT cell development and expansion. J Immunol 191(10):5052-64 |
| abstractText | The invariant NKT (iNKT) cells represent a unique group of alphabeta T cells that have been classified based on their exclusive usage of the invariant Valpha14Jalpha18 TCRalpha-chain and their innate-like effector function. Thus far, the transcriptional programs that control Valpha14Jalpha18 TCRalpha 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 Valpha14 to Jalpha18 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 gammadelta 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. |
