Chronically inflamed human tissues are infiltrated by highly differentiated Th17 lymphocytes
Chronically inflamed human tissues are infiltrated by highly differentiated Th17 lymphocytes
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DOI：
10.4049/jimmunol.180.11.7423
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发表时间：
2008-06-01
影响因子：
4.4
通讯作者：
Gascan, Hugues
中科院分区：
文献类型：
--
作者：
Pene, Jerome;Chevalier, Sylvie;Gascan, Hugues
慢性炎性疾病的特征在于由免疫活性细胞（特别是CD 4（+）T淋巴细胞）引起的局部组织损伤，所述免疫活性细胞通过产生独特的细胞因子组参与这些疾病的发病机制。在这里，我们已经确定了单个CD 4（+）T细胞的特征，这些细胞浸润了银屑病、克罗恩病、类风湿性关节炎或过敏性哮喘患者的炎症组织。细胞因子产生和基因谱分析的结果确定了体内分化的维甲酸相关孤儿受体γ表达T细胞群，产生高水平的IL-17，可代表高达30%的浸润性T淋巴细胞。活化的Th 17细胞产生IL-26、TNF-α、α-光毒素-β和IL-22。组织浸润性Th 17细胞分泌的IL-17和IL-22浓度可达100 nM，与Th 1和Th 2相关细胞因子的产生呈负相关。此外，组织浸润性Th 17细胞的特征还在于CCR 6的高细胞表面表达，CCR 6是一种不被分离自相同病变的Th 1和Th 2细胞表达的趋化因子受体，并且还在于CCL 20/MIP 3 α的产生，CCL 20/MIP 3 α是一种与组织浸润相关的CCR 6配体。从银屑病皮损中分离的活化的Th 17细胞的培养上清液以IL-17和IL-22依赖的方式诱导与炎症和异常角质形成细胞分化相关的基因产物的表达。这些结果表明，组织浸润性Th 17细胞通过产生几种炎性细胞因子和创造有助于它们在炎症部位迁移和隔离的环境而导致人类慢性炎性疾病。
Chronic inflammatory diseases are characterized by local tissue injury caused by immunocompetent cells, in particular CD4(+) T lymphocytes, that are involved in the pathogenesis of these disorders via the production of distinctive sets of cytokines. Here, we have characterized single CD4(+) T cells that infiltrate inflamed tissue taken from patients with psoriasis, Crohn's disease, rheumatoid arthritis, or allergic asthma. Results from a cytokine production and gene profile analysis identified a population of in vivo differentiatedretinoid-related orphan receptor gamma-expressing T cells, producing high levels of IL-17, that can represent up to 30% of infiltrating T lymphocytes. Activated Th17 cells produced IL-26, TNF-alpha, lymphotoxin-beta, and IL-22. IL-17 and IL-22 concentrations secreted by tissue infiltrating Th17 cells could reach up to 100 nM and were inversely correlated with the production of Th1- and Th2-associated cytokines. In addition, tissue-infiltrating Th17 cells are also characterized by high cell surface expression of CCR6, a chemokine receptor that was not expressed by Th1 and Th2 cells, isolated from the same lesions, and by the production of CCL20/MIP3 alpha, a CCR6 ligand, associated with tissue infiltration. Culture supernatants of activated Th17 cells, isolated from psoriatic lesions, induced the expression of gene products associated with inflammation and abnormal keratinocyte differentiation in an IL-17 and IL-22-dependent manner. These results show that tissue-infiltrating Th17 cells contribute to human chronic inflammatory disease via the production of several inflammatory cytokines and the creation of an environment contributing to their migration and sequestration at sites of inflammation.