Foxp3+ regulatory T cells maintain immune homeostasis in the skin

J Exp Med. 2008 Jul 7;205(7):1559-65. doi: 10.1084/jem.20072594. Epub 2008 Jun 23.

Abstract

Cutaneous immune responses must be tightly controlled to prevent unwanted inflammation in response to innocuous antigens, while maintaining the ability to combat skin-tropic pathogens. Foxp3(+) regulatory T (T reg) cells are potent immune regulators and are found at high frequency in both human and mouse skin. Although T reg cells migrate to the skin and can dampen immune responses during experimentally induced inflammation or infection, the importance of cutaneous T reg cells for maintaining normal immune homeostasis in the skin has not been addressed. To selectively block T reg cell function in the skin, we restored the T reg cell compartment in Foxp3-deficient scurfy mice with cells whose ability to migrate to the skin was impaired because of targeted mutation of alpha-1,3-fucosyltransferase VII (Fut7). Although Fut7-deficient T reg cells were present at normal frequency and could function in all other tissues examined, these animals rapidly developed severe cutaneous inflammation. Thus, skin-resident T reg cell are essential for maintaining normal immune homeostasis at this site.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cell Movement / genetics
  • Cell Movement / immunology*
  • Dermatitis / enzymology
  • Dermatitis / genetics
  • Dermatitis / immunology
  • Forkhead Transcription Factors*
  • Fucosyltransferases / genetics
  • Fucosyltransferases / immunology*
  • Fucosyltransferases / metabolism
  • Homeostasis / genetics
  • Homeostasis / immunology*
  • Humans
  • Mice
  • Mice, Knockout
  • Mutation
  • Skin / enzymology
  • Skin / immunology*
  • Skin / pathology
  • T-Lymphocytes, Regulatory / enzymology
  • T-Lymphocytes, Regulatory / immunology*

Substances

  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Fucosyltransferases
  • fucosyltransferase VII, mouse