PMID:21957144

Citation	Shen, S, Chen, Y, Gorentla, BK, Lu, J, Stone, JC and Zhong, XP (2011) Critical roles of RasGRP1 for invariant NKT cell development. J. Immunol. 187:4467-73
Abstract	The invariant NKT (iNKT) cell lineage contains CD4(+) and CD4(-) subsets. The mechanisms that control such subset differentiation and iNKT cell maturation in general have not been fully understood. RasGRP1, a guanine nucleotide exchange factor for TCR-induced activation of the Ras-ERK1/2 pathway, is critical for conventional αβ T cell development but dispensable for generating regulatory T cells. Its role in iNKT cells has been unknown. In this study, we report severe decreases of iNKT cells in RasGRP1(-/-) mice through cell intrinsic mechanisms. In the remaining iNKT cells in RasGRP1(-/-) mice, there is a selective absence of the CD4(+) subset. Furthermore, RasGRP1(-/-) iNKT cells are defective in TCR-induced proliferation in vitro. These observations establish that RasGRP1 is not only important for early iNKT cell development but also for the generation/maintenance of the CD4(+) iNKT cells. Our data provide genetic evidence that the CD4(+) and CD4(-) iNKT cells are distinct sublineages with differential signaling requirements for their development.
Links	PubMed PMC3212869 Online version:10.4049/jimmunol.1003798
Keywords	Animals; Antigens, CD4/biosynthesis; Antigens, CD4/genetics; Cell Differentiation/genetics; Cell Differentiation/immunology; Cell Lineage/genetics; Cell Lineage/immunology; Guanine Nucleotide Exchange Factors/deficiency; Guanine Nucleotide Exchange Factors/genetics; Guanine Nucleotide Exchange Factors/physiology; Lymphopenia/genetics; Lymphopenia/immunology; Lymphopenia/pathology; Mice; Mice, Inbred C57BL; Mice, Knockout; Natural Killer T-Cells/cytology; Natural Killer T-Cells/immunology; Natural Killer T-Cells/metabolism; Receptors, Antigen, T-Cell, alpha-beta/deficiency; Receptors, Antigen, T-Cell, alpha-beta/genetics; Receptors, Antigen, T-Cell, gamma-delta/deficiency; Receptors, Antigen, T-Cell, gamma-delta/genetics; Signal Transduction/genetics; Signal Transduction/immunology
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:GRP1	involved_in	GO:0032825: positive regulation of natural killer cell differentiation	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:GRP1		GO:0032825: positive regulation of natural killer cell differentiation	ECO:0000315:		P		Fig 1D, 1E: RasGRP1 is necessary for early NKC development	complete CACAO 2857
MOUSE:GRP1		GO:0032816: positive regulation of natural killer cell proliferation	ECO:0000315:		P		Fig 3F: lack of natural killer cell proliferation of RasGRP -/- mutant	complete CACAO 2860
MOUSE:GRP1	involved_in	GO:0032816: positive regulation of natural killer cell activation	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

References

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