IL-17+ Regulatory T Cells in the Microenvironments of Chronic Inflammation and Cancer
IL-17+ Regulatory T Cells in the Microenvironments of Chronic Inflammation and Cancer
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DOI：
10.4049/jimmunol.1003251
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发表时间：
2011-04-01
影响因子：
4.4
通讯作者：
Zou, Weiping
中科院分区：
文献类型：
--
作者：
Kryczek, Ilona;Wu, Ke;Zou, Weiping
Foxp3(+)CD4(+) 调节性 T (Treg) 细胞抑制免疫反应并缓和炎症。 IL-17(+)CD4(+) T (Th17) 细胞介导自身免疫性疾病的炎症。在健康人的外周血中观察到少量的 IL-17(+)Foxp3(+)CD4(+) T 细胞。然而，人类对 IL-17(+)Foxp3(+)CD4(+) T 细胞的生物学知之甚少。我们研究了它们在溃疡性结肠炎患者中的表型、细胞因子谱、产生和病理相关性。我们观察到高水平的IL-17(+)Foxp3(+)CD4(+) T细胞选择性地积聚在结肠炎微环境和相关结肠癌中。 IL-17(+)Foxp3(+)CD4(+) T细胞的表型和细胞因子谱与Th17和Treg细胞重叠。骨髓 APC、IL-2 和 TGF-β 对于记忆 CCR6(+) T 细胞或 Treg 细胞的诱导至关重要。 IL-17(+)Foxp3(+)CD4(+) T 细胞功能性抑制 T 细胞活化并刺激结肠炎组织中炎症细胞因子的产生。我们的数据表明IL-17(+)Foxp3(+)细胞可能是病理微环境中的“炎症”Treg细胞。这些细胞可能通过诱导炎症细胞因子和抑制局部 T 细胞免疫来促进溃疡性结肠炎的发病机制，进而可能在机制上将人类慢性炎症与肿瘤的发展联系起来。因此，我们的数据挑战了人们对 Treg 细胞抗炎作用的普遍看法，并表明 Treg 细胞生物学更为复杂，至少在人类慢性炎症和相关癌症的背景下是如此。免疫学杂志，2011，186：4388-4395。
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-beta 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.