title: Increased level of E protein activity during invariant NKT development promotes differentiation of invariant NKT2 and invariant NKT17 subsets.
abstract: E protein transcription factors and their natural inhibitors, Id proteins, play critical and complex roles during lymphoid development. In this article, we report that partial maintenance of E protein activity during positive selection results in a change in the cell fate determination of developing iNKT cells, with a block in the development of iNKT1 cells and a parallel increase in the iNKT2 and iNKT17 subsets. Because the expression levels of the transcription factors that drive these alternative functional fates (GATA-3, RORγT, T-bet, and Runx-3) are not altered, our results suggest that E protein activity controls a novel checkpoint that regulates the number of iNKT precursors that choose each fate.
authors.affiliation: Immunobiology and Cancer Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104.
authors.forename: Taishan
authors.initials: T
authors.lastname: Hu
authors.forename: Hongcheng
authors.initials: H
authors.lastname: Wang
authors.forename: Amie
authors.initials: A
authors.lastname: Simmons
authors.forename: Sandra
authors.initials: S
authors.lastname: Bajaña
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhao
authors.forename: Susan
authors.initials: S
authors.lastname: Kovats
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Sun
authors.forename: Jose
authors.initials: J
authors.lastname: Alberola-Ila
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D002454:Cell Differentiation / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D050677:Core Binding Factor Alpha 3 Subunit / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis; D053646:Interleukin-2 Receptor beta Subunit / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D055611:Natural Killer T-Cells / Q000378:metabolism*; D022661:RNA, Untranslated / Q000235:genetics; D015398:Signal Transduction / Q000276:immunology; D020825:T-Box Domain Proteins / Q000096:biosynthesis; D000098815:T-bet Transcription Factor
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D050677:Core Binding Factor Alpha 3 Subunit; D007371:Interferon-gamma; D053646:Interleukin-2 Receptor beta Subunit; D022661:RNA, Untranslated; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; C110853:Gt(ROSA)26Sor non-coding RNA, mouse; C493730:Runx3 protein, mouse