GATA-3 regulates the development and function of invariant NKT cells.
Although invariant NKT (iNKT) cells participate in many aspects of immune responses, the molecular mechanisms regulating their development, maturation, and activation are still poorly understood. GATA-3 is a T cell-specific transcription factor that is also expressed in iNKT cells. The critical role of GATA-3 in conventional alphabeta T cells has been well documented, but whether GATA-3 also regulates the development and function of iNKT cells is unknown. In the present study, we report that deficiency of GATA-3 results in cell-intrinsic defects in the thymic development and peripheral maturation of murine iNKT cells. In addition, GATA-3 is also required for survival, activation, and effector functions of this unique population of T cells. Our data also reveal a previously unidentified peripheral maturation step that is GATA-3 dependent.
Kim
Peter J
PJ
Division of Rheumatology, Immunology, and Allergy, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
Pai
Sung-Yun
SY
Brigl
Manfred
M
Besra
Gurdyal S
GS
Gumperz
Jenny
J
Ho
I-Cheng
IC
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood; D050990:GATA3 Transcription Factor / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D005699:Galactosylceramides / Q000008:administration & dosage; D007275:Injections, Intravenous; D007371:Interferon-gamma / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000378:metabolism
D016207:Cytokines; D050990:GATA3 Transcription Factor; D005699:Galactosylceramides; C494748:Gata3 protein, mouse; D011948:Receptors, Antigen, T-Cell; C493154:alpha-galactosylceramide; D007371:Interferon-gamma