Altering the distribution of Foxp3(+) regulatory T cells results in tissue-specific inflammatory disease.

J Exp Med 2007 Jun 4;204(6):1335-47. Epub 2007 Jun 4.

Benaroya Research Institute, Seattle, WA 98101, USA.

CD4(+)Foxp3(+) regulatory T cells (T reg) are essential for maintaining self-tolerance, but their functional mechanisms and sites of action in vivo are poorly defined. We examined the homing receptor expression and tissue distribution of T reg cells in the steady state and determined whether altering their distribution by removal of a single chemokine receptor impairs their ability to maintain tissue-specific peripheral tolerance. We found that T reg cells are distributed throughout all nonlymphoid tissues tested, and are particularly prevalent in the skin, where they express a unique CCR4(+)CD103(hi) phenotype. T reg cell expression of CCR4 and CD103 is induced by antigen-driven activation within subcutaneous lymph nodes, and accumulation of T reg cells in the skin and lung airways is impaired in the absence of CCR4 expression. Mice with a complete loss of CCR4 in the T reg cell compartment develop lymphocytic infiltration and severe inflammatory disease in the skin and lungs, accompanied by peripheral lymphadenopathy and increased differentiation of skin-tropic CD4(+)Foxp3(+) T cells. Thus, selectively altering T reg cell distribution in vivo leads to the development of tissue-specific inflammatory disease.

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http://www.jem.org/lookup/doi/10.1084/jem.20070081
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http://dx.doi.org/10.1084/jem.20070081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118615PMC
June 2007
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