TY - JOUR
T1 - IL-17+ regulatory T Cells in the microenvironments of chronic inflammation and cancer
AU - Kryczek, Ilona
AU - Wu, Ke
AU - Zhao, Ende
AU - Wei, Shuang
AU - Vatan, Linhua
AU - Szeliga, Wojciech
AU - Huang, Emina
AU - Greenson, Joel
AU - Chang, Alfred
AU - Roliński, Jacek
AU - Radwan, Piotr
AU - Fang, Jingyuan
AU - Wang, Guobin
AU - Zou, Weiping
PY - 2011/4/1
Y1 - 2011/4/1
N2 - 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-b 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. The Journal of Immunology, 2011, 186: 4388-4395.
AB - 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-b 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. The Journal of Immunology, 2011, 186: 4388-4395.
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U2 - 10.4049/jimmunol.1003251
DO - 10.4049/jimmunol.1003251
M3 - Article
C2 - 21357259
AN - SCOPUS:79955040909
SN - 0022-1767
VL - 186
SP - 4388
EP - 4395
JO - Journal of Immunology
JF - Journal of Immunology
IS - 7
ER -