IL-17+ regulatory T cells in the microenvironments of chronic inflammation and cancer - PubMed (original) (raw)

. 2011 Apr 1;186(7):4388-95.

doi: 10.4049/jimmunol.1003251. Epub 2011 Feb 28.

Ke Wu, Ende Zhao, Shuang Wei, Linhua Vatan, Wojciech Szeliga, Emina Huang, Joel Greenson, Alfred Chang, Jacek Roliński, Piotr Radwan, Jingyuan Fang, Guobin Wang, Weiping Zou

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IL-17+ regulatory T cells in the microenvironments of chronic inflammation and cancer

Ilona Kryczek et al. J Immunol. 2011.

Abstract

Foxp3(+)CD4(+) regulatory T (Treg) cells inhibit immune responses and temper inflammation. IL-17(+)CD4(+) T (Th17) cells mediate inflammation of autoimmune diseases. A small population of IL-17(+)Foxp3(+)CD4(+) T cells has been observed in peripheral blood in healthy human beings. However, the biology of IL-17(+)Foxp3(+)CD4(+) T cells remains poorly understood in humans. We investigated their phenotype, cytokine profile, generation, and pathological relevance in patients with ulcerative colitis. We observed that high levels of IL-17(+)Foxp3(+)CD4(+) T cells were selectively accumulated in the colitic microenvironment and associated colon carcinoma. The phenotype and cytokine profile of IL-17(+)Foxp3(+)CD4(+) T cells was overlapping with Th17 and Treg cells. Myeloid APCs, IL-2, and TGF-β are essential for their induction from memory CCR6(+) T cells or Treg cells. IL-17(+)Foxp3(+)CD4(+) T cells functionally suppressed T cell activation and stimulated inflammatory cytokine production in the colitic tissues. Our data indicate that IL-17(+)Foxp3(+) cells may be "inflammatory" Treg cells in the pathological microenvironments. These cells may contribute to the pathogenesis of ulcerative colitis through inducing inflammatory cytokines and inhibiting local T cell immunity, and in turn may mechanistically link human chronic inflammation to tumor development. Our data therefore challenge commonly held beliefs of the anti-inflammatory role of Treg cells and suggest a more complex Treg cell biology, at least in the context of human chronic inflammation and associated carcinoma.

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