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Id3 Restricts γδ NKT Cell Expansion by Controlling Egr2 and c-Myc Activity.

Publication ,  Journal Article
Zhang, B; Jiao, A; Dai, M; Wiest, DL; Zhuang, Y
Published in: J Immunol
September 1, 2018

γδ NKT cells are neonatal-derived γδ T lymphocytes that are grouped together with invariant NKT cells based on their shared innate-like developmental program characterized by the transcription factor PLZF (promyelocytic leukemia zinc finger). Previous studies have demonstrated that the population size of γδ NKT cells is tightly controlled by Id3-mediated inhibition of E-protein activity in mice. However, how E proteins promote γδ NKT cell development and expansion remains to be determined. In this study, we report that the transcription factor Egr2, which also activates PLZF expression in invariant NKT cells, is essential for regulating γδ NKT cell expansion. We observed a higher expression of Egr family genes in γδ NKT cells compared with the conventional γδ T cell population. Loss of function of Id3 caused an expansion of γδ NKT cells, which is accompanied by further upregulation of Egr family genes as well as PLZF. Deletion of Egr2 in Id3-deficient γδ NKT cells prevented cell expansion and blocked PLZF upregulation. We further show that this Egr2-mediated γδ NKT cell expansion is dependent on c-Myc. c-Myc knockdown attenuated the proliferation of Id3-deficient γδ NKT cells, whereas c-Myc overexpression enhanced the proliferation of Id3/Egr2-double-deficient γδ NKT cells. Therefore, our data reveal a regulatory circuit involving Egr2-Id3-E2A, which normally restricts the population size of γδ NKT cells by adjusting Egr2 dosage and c-Myc expression.

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Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

September 1, 2018

Volume

201

Issue

5

Start / End Page

1452 / 1459

Location

United States

Related Subject Headings

  • Receptors, Antigen, T-Cell, gamma-delta
  • Proto-Oncogene Proteins c-myc
  • Promyelocytic Leukemia Zinc Finger Protein
  • Natural Killer T-Cells
  • Mice, Knockout
  • Mice
  • Inhibitor of Differentiation Proteins
  • Immunology
  • Gene Expression Regulation
  • Early Growth Response Protein 2
 

Citation

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ICMJE
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Zhang, B., Jiao, A., Dai, M., Wiest, D. L., & Zhuang, Y. (2018). Id3 Restricts γδ NKT Cell Expansion by Controlling Egr2 and c-Myc Activity. J Immunol, 201(5), 1452–1459. https://doi.org/10.4049/jimmunol.1800106
Zhang, Baojun, Anjun Jiao, Meifang Dai, David L. Wiest, and Yuan Zhuang. “Id3 Restricts γδ NKT Cell Expansion by Controlling Egr2 and c-Myc Activity.J Immunol 201, no. 5 (September 1, 2018): 1452–59. https://doi.org/10.4049/jimmunol.1800106.
Zhang B, Jiao A, Dai M, Wiest DL, Zhuang Y. Id3 Restricts γδ NKT Cell Expansion by Controlling Egr2 and c-Myc Activity. J Immunol. 2018 Sep 1;201(5):1452–9.
Zhang, Baojun, et al. “Id3 Restricts γδ NKT Cell Expansion by Controlling Egr2 and c-Myc Activity.J Immunol, vol. 201, no. 5, Sept. 2018, pp. 1452–59. Pubmed, doi:10.4049/jimmunol.1800106.
Zhang B, Jiao A, Dai M, Wiest DL, Zhuang Y. Id3 Restricts γδ NKT Cell Expansion by Controlling Egr2 and c-Myc Activity. J Immunol. 2018 Sep 1;201(5):1452–1459.

Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

September 1, 2018

Volume

201

Issue

5

Start / End Page

1452 / 1459

Location

United States

Related Subject Headings

  • Receptors, Antigen, T-Cell, gamma-delta
  • Proto-Oncogene Proteins c-myc
  • Promyelocytic Leukemia Zinc Finger Protein
  • Natural Killer T-Cells
  • Mice, Knockout
  • Mice
  • Inhibitor of Differentiation Proteins
  • Immunology
  • Gene Expression Regulation
  • Early Growth Response Protein 2