Sather Blythe D, Treuting Piper, Perdue Nikole, Miazgowicz Mike, Fontenot Jason D, Rudensky Alexander Y, Campbell Daniel J
Benaroya Research Institute, Seattle, WA 98101, USA.
J Exp Med. 2007 Jun 11;204(6):1335-47. doi: 10.1084/jem.20070081. Epub 2007 Jun 4.
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.
CD4(+)Foxp3(+)调节性T细胞（Treg）对于维持自身耐受性至关重要，但其在体内的功能机制和作用位点尚不清楚。我们研究了稳态下Treg细胞的归巢受体表达和组织分布，并确定通过去除单一趋化因子受体来改变其分布是否会损害它们维持组织特异性外周耐受性的能力。我们发现Treg细胞分布于所有测试的非淋巴组织中，在皮肤中尤为普遍，在那里它们表达独特的CCR4(+)CD103(hi)表型。Treg细胞CCR4和CD103的表达是由皮下淋巴结内抗原驱动的活化诱导的，在缺乏CCR4表达的情况下，Treg细胞在皮肤和肺气道中的积累会受损。Treg细胞区室中CCR4完全缺失的小鼠会在皮肤和肺部发生淋巴细胞浸润和严重的炎症性疾病，伴有外周淋巴结病以及皮肤嗜性CD4(+)Foxp3(+)T细胞分化增加。因此，在体内选择性改变Treg细胞分布会导致组织特异性炎症性疾病的发生。
