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Circulating Th17, Th22, and Th1 Cells Are Increased in Psoriasis

银屑病 白细胞介素17 白细胞介素22 细胞因子 免疫学 流式细胞术 医学 肿瘤坏死因子α 炎症 干扰素γ RAR相关孤儿受体γ C-C趋化因子受体6型 外周血单个核细胞 白细胞介素23 白细胞介素 发病机制 趋化因子 趋化因子受体
作者
Shinji Kagami,Heather L. Rizzo,Jennifer J. Lee,Yoshinobu Koguchi,Andrew Blauvelt
出处
期刊:Journal of Investigative Dermatology [Elsevier]
卷期号:130 (5): 1373-1383 被引量:531
标识
DOI:10.1038/jid.2009.399
摘要

Th17, Th22, and Th1 cells are detected in psoriatic skin lesions and implicated in psoriasis pathogenesis, but inflammatory T cell numbers in blood, as well as the relative importance of each cell type, is unclear. Using 7-color flow cytometry, circulating Th17, Th22, and Th1 cells were quantified in 21 untreated psoriatics and 17 healthy individuals. CCR6 was the best cell surface marker for IL-17A+ cells when compared with IL-23R or CD161. CCR6+, IL-17A+, IL-22+, CCR6+IL-17A+, CCR6+IL-22+, CCR6+tumor necrosis factor-α+, IL-17A+IFN-γ-, IL-17A+IL-22+IFN-γ-, and IL-17A+IL-22-IFN-γ- cells were increased in psoriatics (all values P<0.001), indicating elevations in circulating Th17 cells, using multiple criteria to define these cells. Th22 (IL-17A-IL-22+IFN-γ-, P<0.05) and Th1 (IL-17A-IFN-γ+, P<0.05) cells were also increased in psoriatics, but to a lesser extent. Inhibition of either NF-κB or STAT3 in vitro blocked cytokine production by both Th17 and Th1 cells. Circulating levels of Th17 and Th1 cells decreased in a subset of five psoriasis patients serially evaluated following induction therapy with infliximab. In summary, elevated numbers of circulating inflammatory T cells may contribute to cutaneous inflammation and systemic inflammatory disease that occurs in individuals with psoriasis. Th17, Th22, and Th1 cells are detected in psoriatic skin lesions and implicated in psoriasis pathogenesis, but inflammatory T cell numbers in blood, as well as the relative importance of each cell type, is unclear. Using 7-color flow cytometry, circulating Th17, Th22, and Th1 cells were quantified in 21 untreated psoriatics and 17 healthy individuals. CCR6 was the best cell surface marker for IL-17A+ cells when compared with IL-23R or CD161. CCR6+, IL-17A+, IL-22+, CCR6+IL-17A+, CCR6+IL-22+, CCR6+tumor necrosis factor-α+, IL-17A+IFN-γ-, IL-17A+IL-22+IFN-γ-, and IL-17A+IL-22-IFN-γ- cells were increased in psoriatics (all values P<0.001), indicating elevations in circulating Th17 cells, using multiple criteria to define these cells. Th22 (IL-17A-IL-22+IFN-γ-, P<0.05) and Th1 (IL-17A-IFN-γ+, P<0.05) cells were also increased in psoriatics, but to a lesser extent. Inhibition of either NF-κB or STAT3 in vitro blocked cytokine production by both Th17 and Th1 cells. Circulating levels of Th17 and Th1 cells decreased in a subset of five psoriasis patients serially evaluated following induction therapy with infliximab. In summary, elevated numbers of circulating inflammatory T cells may contribute to cutaneous inflammation and systemic inflammatory disease that occurs in individuals with psoriasis. Psoriasis Area and Severity Index
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