title: 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 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.
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, NC 27710;
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.forename: Di
authors.initials: D
authors.lastname: Wu
authors.forename: Ning
authors.initials: N
authors.lastname: Jiang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhuang
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D015704:CD4 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D051797:Inhibitor of Differentiation Protein 2 / Q000235:genetics*; D051796:Inhibitor of Differentiation Proteins / Q000235:genetics*; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D055611:Natural Killer T-Cells / Q000378:metabolism*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D015704:CD4 Antigens; D016827:CD8 Antigens; D051797:Inhibitor of Differentiation Protein 2; D051796:Inhibitor of Differentiation Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; C497452:Idb2 protein, mouse; C067679:Idb3 protein, mouse