GATA-3 was first cloned as a T cell specific transcription factor in 1991 and its importance in the transcriptional control of T helper type 2 cell (Th2) differentiation was established in the mid to late 90's. A r...GATA-3 was first cloned as a T cell specific transcription factor in 1991 and its importance in the transcriptional control of T helper type 2 cell (Th2) differentiation was established in the mid to late 90's. A role for GATA-3 during thymic development has long implied by its continuous and regulated expression through out T lineage development, but the absolute requirement for GATA-3 during early T lymphoid commitment/survival previously precluded definitive answers to this question. Several technical breakthroughs have fueled fruitful investigation in recent years and uncovered unexpected and critical roles for GATA-3 in CD4 thymocyte survival, invariant natural killer T cell generation and function, and also in beta selection. Not only does GATA-3 participate in nearly every stage of T cell development from common lymphoid progenitor to Th2, conditional knockout studies have indicated that the influence of GATA-3 also extends beyond the immune system. Cellular & Molecular Immunology. 2007; 4(1): 15-29.展开更多
The transcription factor Ets1 is essential for the development of invariant natural killer T(iNKT)cells;however,its detailed role and mechanism of action are unknown.Here,we show that Ets1 is dispensable for CD1d-medi...The transcription factor Ets1 is essential for the development of invariant natural killer T(iNKT)cells;however,its detailed role and mechanism of action are unknown.Here,we show that Ets1 is dispensable for CD1d-mediated selection,but is essential for subsequent differentiation of post-selected iNKT cells.This function is partly compensated by forced expression of a transgenic Vα14 Jα18 TCR and is independent of its N-terminal Pointed(PNT)domain.Ets1 is also required for optimal expression of cytokines by differentiated iNKT1 and iNKT2 cells,but inhibits the differentiation/function of iNKT17 in vitro and in vivo.These functions,however,depend on the PNT domain.Taken together,our results indicate that Ets1 regulates the differentiation/function of iNKT cells at multiple steps through both PNT domaindependent and PNT domain-independent mechanisms.展开更多
文摘GATA-3 was first cloned as a T cell specific transcription factor in 1991 and its importance in the transcriptional control of T helper type 2 cell (Th2) differentiation was established in the mid to late 90's. A role for GATA-3 during thymic development has long implied by its continuous and regulated expression through out T lineage development, but the absolute requirement for GATA-3 during early T lymphoid commitment/survival previously precluded definitive answers to this question. Several technical breakthroughs have fueled fruitful investigation in recent years and uncovered unexpected and critical roles for GATA-3 in CD4 thymocyte survival, invariant natural killer T cell generation and function, and also in beta selection. Not only does GATA-3 participate in nearly every stage of T cell development from common lymphoid progenitor to Th2, conditional knockout studies have indicated that the influence of GATA-3 also extends beyond the immune system. Cellular & Molecular Immunology. 2007; 4(1): 15-29.
基金supported by grants from the United States Department of Defense(W81XWH-11-1-0492 to I.-C.H.)the National Institutes of Health(AR070171 to I.-C.H.and HL082717 to P.O.)+1 种基金the Ministry of Science and Technology(103-2311-B-650-001 and 105-2311-B-214-002 to T.-S.T.),TaiwanEDa Hospital(103-EDN16,104-EDN12,105-EDN07,and EDAHI105002 to T.-S.T.),Taiwan.
文摘The transcription factor Ets1 is essential for the development of invariant natural killer T(iNKT)cells;however,its detailed role and mechanism of action are unknown.Here,we show that Ets1 is dispensable for CD1d-mediated selection,but is essential for subsequent differentiation of post-selected iNKT cells.This function is partly compensated by forced expression of a transgenic Vα14 Jα18 TCR and is independent of its N-terminal Pointed(PNT)domain.Ets1 is also required for optimal expression of cytokines by differentiated iNKT1 and iNKT2 cells,but inhibits the differentiation/function of iNKT17 in vitro and in vivo.These functions,however,depend on the PNT domain.Taken together,our results indicate that Ets1 regulates the differentiation/function of iNKT cells at multiple steps through both PNT domaindependent and PNT domain-independent mechanisms.