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A function for IL-7R for CD4+CD25+Foxp3+ T regulatory cells

Academic Article
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Overview

related to degree

  • Lee, Joon Youb, Ph.D. in Biology, Scripps Research 2003 - 2009

authors

  • Bayer, A. L.
  • Lee, Joon Youb
  • de la Barrera, A.
  • Surh, Charles
  • Malek, T. R.

publication date

  • July 2008

journal

  • Journal of Immunology  Journal

abstract

  • The IL-2/IL-2R interaction is important for development and peripheral homeostasis of T regulatory (Treg) cells. IL-2- and IL-2R-deficient mice are not completely devoid of Foxp3+ cells, but rather lack population of mature CD4+CD25+Foxp3high Treg cells and contain few immature CD4+CD25-Foxp3low T cells. Interestingly, common gamma chain (gammac) knockout mice have been shown to have a near complete absence of Foxp3+ Treg cells, including the immature CD25-Foxp3low subset. Therefore, other gammac-cytokine(s) must be critically important during thymic development of CD4+CD25+Foxp3+ Treg cells apart from the IL-2. The present study was undertaken to determine whether the gammac-cytokines IL-7 or IL-15 normally contribute to expression of Foxp3 and Treg cell production. These studies revealed that mice double deficient in IL-2Rbeta and IL-7Ralpha contained a striking lack in the CD4+Foxp3+ population and the Treg cell defect recapitulated the gammac knockout mice. In the absence of IL-7R signaling, IL-15/IL-15R interaction is dispensable for the production of CD4+CD25+Foxp3+ Treg cells, indicating that normal thymic Treg cell production likely depends on signaling through both IL-2 and IL-7 receptors. Selective thymic reconstitution of IL-2Rbeta in mice double deficient in IL-2Rbeta and IL-7Ralpha established that IL-2Rbeta is dominant and sufficient to restore production of Treg cells. Furthermore, the survival of peripheral CD4+Foxp3low cells in IL-2Rbeta-/- mice appears to depend upon IL-7R signaling. Collectively, these data indicate that IL-7R signaling contributes to Treg cell development and peripheral homeostasis.

subject areas

  • Animals
  • Cell Differentiation
  • Forkhead Transcription Factors
  • Gene Expression Regulation
  • Homeostasis
  • Interleukin-2
  • Interleukin-2 Receptor alpha Subunit
  • Interleukin-7
  • Mice
  • Mice, Knockout
  • Receptors, Interleukin-2
  • Receptors, Interleukin-7
  • T-Lymphocytes, Regulatory
  • Thymus Gland
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Identity

PubMed Central ID

  • PMC2601574

International Standard Serial Number (ISSN)

  • 0022-1767

PubMed ID

  • 18566388
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Additional Document Info

start page

  • 225

end page

  • 234

volume

  • 181

issue

  • 1

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