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Critical roles of RasGRP1 for invariant NKT cell development.

Publication ,  Journal Article
Shen, S; Chen, Y; Gorentla, BK; Lu, J; Stone, JC; Zhong, X-P
Published in: Journal of immunology (Baltimore, Md. : 1950)
November 2011

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.

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Published In

Journal of immunology (Baltimore, Md. : 1950)

DOI

EISSN

1550-6606

ISSN

0022-1767

Publication Date

November 2011

Volume

187

Issue

9

Start / End Page

4467 / 4473

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

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Shen, S., Chen, Y., Gorentla, B. K., Lu, J., Stone, J. C., & Zhong, X.-P. (2011). Critical roles of RasGRP1 for invariant NKT cell development. Journal of Immunology (Baltimore, Md. : 1950), 187(9), 4467–4473. https://doi.org/10.4049/jimmunol.1003798
Shen, Shudan, Yong Chen, Balachandra K. Gorentla, Jianxin Lu, James C. Stone, and Xiao-Ping Zhong. “Critical roles of RasGRP1 for invariant NKT cell development.Journal of Immunology (Baltimore, Md. : 1950) 187, no. 9 (November 2011): 4467–73. https://doi.org/10.4049/jimmunol.1003798.
Shen S, Chen Y, Gorentla BK, Lu J, Stone JC, Zhong X-P. Critical roles of RasGRP1 for invariant NKT cell development. Journal of immunology (Baltimore, Md : 1950). 2011 Nov;187(9):4467–73.
Shen, Shudan, et al. “Critical roles of RasGRP1 for invariant NKT cell development.Journal of Immunology (Baltimore, Md. : 1950), vol. 187, no. 9, Nov. 2011, pp. 4467–73. Epmc, doi:10.4049/jimmunol.1003798.
Shen S, Chen Y, Gorentla BK, Lu J, Stone JC, Zhong X-P. Critical roles of RasGRP1 for invariant NKT cell development. Journal of immunology (Baltimore, Md : 1950). 2011 Nov;187(9):4467–4473.

Published In

Journal of immunology (Baltimore, Md. : 1950)

DOI

EISSN

1550-6606

ISSN

0022-1767

Publication Date

November 2011

Volume

187

Issue

9

Start / End Page

4467 / 4473

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