Critical roles of RasGRP1 for invariant NKT cell development.
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.
Duke Scholars
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Related Subject Headings
- Signal Transduction
- Receptors, Antigen, T-Cell, gamma-delta
- Receptors, Antigen, T-Cell, alpha-beta
- Natural Killer T-Cells
- Mice, Knockout
- Mice, Inbred C57BL
- Mice
- Lymphopenia
- Immunology
- Guanine Nucleotide Exchange Factors
Citation
Published In
DOI
EISSN
ISSN
Publication Date
Volume
Issue
Start / End Page
Related Subject Headings
- Signal Transduction
- Receptors, Antigen, T-Cell, gamma-delta
- Receptors, Antigen, T-Cell, alpha-beta
- Natural Killer T-Cells
- Mice, Knockout
- Mice, Inbred C57BL
- Mice
- Lymphopenia
- Immunology
- Guanine Nucleotide Exchange Factors