CaltechAUTHORS
Published April 1, 2011 | Version Accepted Version
Journal Article Open

Regulation of GATA-3 Expression during CD4 Lineage Differentiation

Creators

  • 1. ROR icon Oklahoma Medical Research Foundation
  • 2. ROR icon California Institute of Technology
  • 3. ROR icon Research Institute of Molecular Pathology
  • 4. ROR icon University of Virginia
  • 5. ROR icon University of Oklahoma Health Sciences Center

Abstract

GATA-3 is necessary for the development of MHC class II-restricted CD4 T cells, and its expression is increased during positive selection of these cells. TCR signals drive this upregulation, but the signaling pathways that control this process are not well understood. Using genetic and pharmacological approaches, we show that GATA-3 upregulation during thymocyte-positive selection is the result of additive inputs from the Ras/MAPK and calcineurin pathways. This upregulation requires the presence of the transcription factor c-Myb. Furthermore, we show that TH-POK can also upregulate GATA-3 in double-positive thymocytes, suggesting the existence of a positive feedback loop that contributes to lock in the initial commitment to the CD4 lineage during differentiation.

Additional Information

© 2011 American Association of Immunologists, Inc. Received October 22, 2010; Accepted January 20, 2011. Published online before print February 25, 2011. This work was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (Grant AI059302 to J.A.-I.), the American Heart Association (Grant 0855002F to J.A.-I.), and a grant from the Spanish Education and Science Department (to I.G.). We thank Drs. D. Straus, J. Downward, F. Macian, D. Cantrell, A. Weiss, J. Pomerantz, and D. Kappes for providing reagents and animals and S. Kovats (Oklahoma Medical Research Foundation) for discussions.

Attached Files

Accepted Version - nihms267983.pdf

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Additional details

Identifiers

PMCID
PMC3074202
Eprint ID
23273
Resolver ID
CaltechAUTHORS:20110411-105608478

Funding

NIH
AI059302
American Heart Association
0855002F
Ministerio de Educación y Ciencia (MEC)

Dates

Created
2011-04-12
Created from EPrint's datestamp field
Updated
2021-11-09
Created from EPrint's last_modified field