B7-H1-expressing antigen-presenting cells mediate polarization of protumorigenic Th22 subsets
B7-H1-expressing antigen-presenting cells mediate polarization of protumorigenic Th22 subsets
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表达 B7-H1 的抗原呈递细胞介导促肿瘤 Th22 亚群的极化
DOI：
10.1172/jci74381
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发表时间：
2014-10-01
影响因子：
15.9
通讯作者：
Zheng, Limin
中科院分区：
文献类型：
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作者：
Kuang, Dong-Ming;Xiao, Xiao;Zheng, Limin
经典的产生IL-22的T辅助细胞（Th 22细胞）独立于IFN-γ和IL-17介导炎症反应;然而，最近已经鉴定出非经典的Th 22细胞，其与IL-22共表达IFN-γ和/或IL-17沿着。关于经典和非经典Th 22亚群在人类疾病中是如何调节的知之甚少。在这里，我们使用人类血液，正常和瘤周肝脏，和肝细胞癌（HCC）的样本来描绘各种Th 22亚群的表型，分布，生成和功能相关性。三个非经典的Th 22亚群构成了人肝和HCC组织中所有Th 22细胞的大多数，尽管经典的Th 22亚群在血液中占主导地位。由TLR 2和TLR 4激动剂激活的单核细胞充当抗原呈递细胞（APC），其最有效地触发来自记忆T细胞的非经典Th 22亚群和来自初始T细胞的经典Th 22亚群的扩增。此外，表达B7-H1的单核细胞通过与程序性死亡1（PD-1）的相互作用使Th 22极化偏离IFN-γ并朝向IL-17，这种作用可以为体内侵袭性癌症生长和血管生成创造有利条件。我们的研究结果提供了对Th 22亚群的选择性调节的见解，并表明影响炎症细胞功能活动的策略可能有利于抗癌治疗。
Classical IL-22-producing T helper cells (Th22 cells) mediate inflammatory responses independently of IFN-gamma and IL-17; however, nonclassical Th22 cells have been recently identified and coexpress IFN-gamma and/or IL-17 along with IL-22. Little is known about how classical and nonclassical Th22 subsets in human diseases are regulated. Here, we used samples of human blood, normal and peritumoral liver, and hepatocellular carcinoma (HCC) to delineate the phenotype, distribution, generation, and functional relevance of various Th22 subsets. Three nonclassical Th22 subsets constituted the majority of all Th22 cells in human liver and HCC tissues, although the classical Th22 subset was predominant in blood. Monocytes activated by TLR2 and TLR4 agonists served as the antigen-presenting cells (APCs) that most efficiently triggered the expansion of nonclassical Th22 subsets from memory T cells and classical Th22 subsets from naive T cells. Moreover, B7-H1-expressing monocytes skewed Th22 polarization away from IFN-gamma and toward IL-17 through interaction with programmed death 1 (PD-1), an effect that can create favorable conditions for in vivo aggressive cancer growth and angiogenesis. Our results provide insight into the selective modulation of Th22 subsets and suggest that strategies to influence functional activities of inflammatory cells may benefit anticancer therapy.