Critical Roles of RasGRP1 for Invariant NKT Cell Development
| Autor: | Shudan Shen, Xiao-Ping Zhong, James C. Stone, Jianxin Lu, Yong Chen, Balachandra K. Gorentla |
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| Rok vydání: | 2011 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 187:4467-4473 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.1003798 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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