Foxp3+ regulatory T cells maintain immune homeostasis in the skin.
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.
Benaroya Research Institute, Seattle, WA 98101, USA.
Jan C
JC
Dudda
Nikole
N
Perdue
Eva
E
Bachtanian
Daniel J
DJ
Campbell
D000818:Animals; D002465:Cell Movement / Q000235:genetics / Q000276:immunology*; D003872:Dermatitis / Q000201:enzymology / Q000235:genetics / Q000276:immunology; D051858:Forkhead Transcription Factors; D005647:Fucosyltransferases / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006706:Homeostasis / Q000235:genetics / Q000276:immunology*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D012867:Skin / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000201:enzymology / Q000276:immunology*
D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D005647:Fucosyltransferases; C514210:fucosyltransferase VII, mouse