Interleukin-7 influences FOXP3+CD4+ regulatory T cells peripheral homeostasis

PLoS One. 2012;7(5):e36596. doi: 10.1371/journal.pone.0036596. Epub 2012 May 7.

Abstract

Mechanisms governing peripheral CD4+ FOXP3+ regulatory T cells (Treg) survival and homeostasis are multiple suggesting tight and complex regulation of regulatory T cells homeostasis. Some specific factors, such as TGF-β, interleukin-2 (IL-2) and B7 costimulatory molecules have been identified as essentials for maintenance of the peripheral Treg compartment. Conversely, Treg dependency upon classical T cell homeostatic factors such as IL-7 is still unclear. In this work, we formally investigated the role of IL-7 in Treg homeostasis in vivo in murine models. We demonstrated that IL-7 availability regulated the size of peripheral Treg cell pool and thus paralleled the impact of IL-7 on conventional T cell pool. Moreover, we showed that IL-7 administration increased Treg cell numbers by inducing thymic-independent Treg peripheral expansion. Importantly the impact of IL-7 on Treg expansion was detected whether conventional T cells were present or absent as IL-7 directly participates to the peripheral expansion of Treg after adoptive transfer into lymphopenic hosts. Our results definitively identify IL-7 as a central factor contributing to Treg peripheral homeostasis, thus reassembling Treg to other T cell subsets in respect of their need for IL-7 for their peripheral maintenance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / metabolism*
  • Cell Proliferation
  • Cell Size
  • Forkhead Transcription Factors / metabolism
  • Homeodomain Proteins / genetics
  • Homeostasis / genetics
  • Interleukin-2 / metabolism
  • Interleukin-7* / administration & dosage
  • Interleukin-7* / genetics
  • Interleukin-7* / metabolism
  • Lymphopenia / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Signal Transduction / genetics
  • T-Lymphocytes, Regulatory* / cytology
  • T-Lymphocytes, Regulatory* / drug effects
  • T-Lymphocytes, Regulatory* / metabolism
  • Thymus Gland* / growth & development
  • Thymus Gland* / metabolism

Substances

  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Homeodomain Proteins
  • Interleukin-2
  • Interleukin-7
  • RAG-1 protein