Directing traffic on the NKT-cell highway: a key role for ThPOK.
CD1d-restricted NKT cells include CD4(+) and DN subsets, with an additional CD8(+) subset that is present in humans but not in mice. The molecular regulation of CD4/CD8 expression by NKT cells, and differentiation of these NKT-cell subsets, is poorly understood. The transcription factors GATA3 and ThPOK regulate lineage commitment of conventional MHC class II-restricted CD4(+) T cells; however, their role in CD4/CD8 expression by CD1d-restricted NKT cells is less clear. A new study in this issue of the European Journal of Immunology demonstrates a key role for ThPOK in differentiation of NKT-cell subsets. This study reveals that GATA3 and ThPOK are necessary for the development of CD4(+) NKT cells. Furthermore, ThPOK-deficient mice generate an unusual population of CD8(+) NKT cells, which are absent in control mice. This study sheds new light on the underlying molecular events leading to the emergence of distinct NKT-cell subsets.
Chakravarti
Sumone
S
Department of Microbiology and Immunology, University of Melbourne, Parkville, VIC, Australia. sumonec@unimelb.edu.au
Godfrey
Dale I
DI
D000818:Animals; D015704:CD4 Antigens / Q000235:genetics / Q000378:metabolism; D016827:CD8 Antigens / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D019070:Cell Lineage / Q000235:genetics / Q000276:immunology; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D016131:Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D015704:CD4 Antigens; D016827:CD8 Antigens; D050990:GATA3 Transcription Factor; D014157:Transcription Factors; C494748:Gata3 protein, mouse; C497211:Zbtb7b protein, mouse