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Combined deletion of Id2 and Id3 genes reveals multiple roles for E proteins in invariant NKT cell development and expansion.

Publication ,  Journal Article
Li, J; Wu, D; Jiang, N; Zhuang, Y
Published in: J Immunol
November 15, 2013

The invariant NKT (iNKT) cells represent a unique group of αβ T cells that have been classified based on their exclusive usage of the invariant Vα14Jα18 TCRα-chain and their innate-like effector function. Thus far, the transcriptional programs that control Vα14Jα18 TCRα rearrangements and the population size of iNKT cells are still incompletely defined. E protein transcription factors have been shown to play necessary roles in the development of multiple T cell lineages, including iNKT cells. In this study, we examined E protein functions in T cell development through combined deletion of genes encoding E protein inhibitors Id2 and Id3. Deletion of Id2 and Id3 in T cell progenitors resulted in a partial block at the pre-TCR selection checkpoint and a dramatic increase in numbers of iNKT cells. The increase in iNKT cells is accompanied with a biased rearrangement involving Vα14 to Jα18 recombination at the double-positive stage and enhanced proliferation of iNKT cells. We further demonstrate that a 50% reduction of E proteins can cause a dramatic switch from iNKT to innate-like γδ T cell fate in Id2- and Id3-deficient mice. Collectively, these findings suggest that Id2- and Id3-mediated inhibition of E proteins controls iNKT development by restricting lineage choice and population expansion.

Duke Scholars

Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

November 15, 2013

Volume

191

Issue

10

Start / End Page

5052 / 5064

Location

United States

Related Subject Headings

  • Receptors, Antigen, T-Cell, alpha-beta
  • Natural Killer T-Cells
  • Mice, Transgenic
  • Mice, Inbred C57BL
  • Mice
  • Lymphocyte Count
  • Inhibitor of Differentiation Proteins
  • Inhibitor of Differentiation Protein 2
  • Immunology
  • Cell Proliferation
 

Citation

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Li, J., Wu, D., Jiang, N., & Zhuang, Y. (2013). Combined deletion of Id2 and Id3 genes reveals multiple roles for E proteins in invariant NKT cell development and expansion. J Immunol, 191(10), 5052–5064. https://doi.org/10.4049/jimmunol.1301252
Li, Jia, Di Wu, Ning Jiang, and Yuan Zhuang. “Combined deletion of Id2 and Id3 genes reveals multiple roles for E proteins in invariant NKT cell development and expansion.J Immunol 191, no. 10 (November 15, 2013): 5052–64. https://doi.org/10.4049/jimmunol.1301252.
Li, Jia, et al. “Combined deletion of Id2 and Id3 genes reveals multiple roles for E proteins in invariant NKT cell development and expansion.J Immunol, vol. 191, no. 10, Nov. 2013, pp. 5052–64. Pubmed, doi:10.4049/jimmunol.1301252.

Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

November 15, 2013

Volume

191

Issue

10

Start / End Page

5052 / 5064

Location

United States

Related Subject Headings

  • Receptors, Antigen, T-Cell, alpha-beta
  • Natural Killer T-Cells
  • Mice, Transgenic
  • Mice, Inbred C57BL
  • Mice
  • Lymphocyte Count
  • Inhibitor of Differentiation Proteins
  • Inhibitor of Differentiation Protein 2
  • Immunology
  • Cell Proliferation