The transcription factor c-Myb primes CD4+CD8+ immature thymocytes for selection into the iNKT lineage.
Type I invariant NKT cells (iNKT cells) are a subset of alphabeta T cells characterized by the expression of an invariant alpha-chain variable region 14-alpha-chain joining region 18 (V(alpha)14J(alpha)18) T cell antigen receptor (TCR) alpha-chain. The iNKT cells derive from CD4(+)CD8(+) double-positive (DP) thymocytes, and their generation requires a long half-life of DP thymocytes to allow V(alpha)14-J(alpha)18 rearrangements, expression of glycolipid-loaded CD1d on DP thymocytes, and signaling through the signaling-activation molecule SLAM-adaptor SAP pathway. Here we show that the transcription factor c-Myb has a central role in priming DP thymocytes to enter the iNKT lineage by simultaneously regulating CD1d expression, the half-life of DP cells and expression of SLAMF1, SLAMF6 and SAP.
Hu
Taishan
T
Immunobiology and Cancer Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
Simmons
Amie
A
Yuan
Joan
J
Bender
Timothy P
TP
Alberola-Ila
Jose
J
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D055610:Antigens, CD1d / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016026:Bone Marrow Transplantation; D015704:CD4 Antigens / Q000096:biosynthesis; D016827:CD8 Antigens / Q000096:biosynthesis; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D019070:Cell Lineage / Q000235:genetics / Q000276:immunology; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D050990:GATA3 Transcription Factor / Q000235:genetics; D015329:Gene Rearrangement, T-Lymphocyte / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D055611:Natural Killer T-Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D054504:Precursor Cells, T-Lymphoid / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D020598:Proto-Oncogene Proteins c-myb / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011828:Radiation Chimera; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D049231:Saposins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D000071176:Signaling Lymphocytic Activation Molecule Family; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D013950:Thymus Gland / Q000166:cytology; D051020:bcl-X Protein / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D015703:Antigens, CD; D055610:Antigens, CD1d; C494812:Bcl2l1 protein, mouse; D015704:CD4 Antigens; D016827:CD8 Antigens; D050990:GATA3 Transcription Factor; D020598:Proto-Oncogene Proteins c-myb; D011956:Receptors, Cell Surface; D049231:Saposins; D000071176:Signaling Lymphocytic Activation Molecule Family; C000604062:Slamf1 protein, mouse; C000604063:Slamf6 protein, mouse; D051020:bcl-X Protein; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1
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