IL-22-producing "T22" T cells account for upregulated IL-22 in atopic dermatitis despite reduced IL-17-producing TH17 T cells.

IL-22-producing "T22" T cells account for upregulated IL-22 in atopic dermatitis despite reduced IL-17-producing TH17 T cells.
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DOI:
10.1016/j.jaci.2009.03.041
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发表时间:
2009-06
影响因子:
14.2
通讯作者:
Guttman-Yassky, Emma
Guttman-Yassky, Emma
中科院分区:
医学1区
文献类型:
--
作者:
Nograles, Kristine E.;Zaba, Lisa C.;Shemer, Avner;Fuentes-Duculan, Judilyn;Cardinale, Irma;Kikuchi, Toyoko;Ramon, Michal;Bergman, Reuven;Krueger, James G.;Guttman-Yassky, Emma

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银屑病和特应性皮炎(AD)是常见的炎症性皮肤病。银屑病患者Th 17/IL-23通路表达上调。尽管在急性疾病期间提示了Th 17 T细胞在AD中的潜在参与,但这些细胞在慢性AD中的作用仍不清楚。研究这些疾病之间IL-23/Th 17信号的差异,并建立AD中T细胞亚群的相对频率。从慢性AD(n=12)和银屑病(n=13)患者收集皮肤活检和外周血。通过细胞内细胞因子染色和流式细胞术检查这两个隔室中的CD 4+和CD 8 + T细胞亚群的相对频率。在外周血中,不同疾病之间的T细胞亚群的百分比没有显着差异。相比之下,银屑病皮肤与AD相比,Th 1和Th 17 T细胞的频率显著增加,而Th 2 T细胞在AD中显著升高。与银屑病相比,AD皮肤中产生不同IL-22的CD 4+和CD 8 + T细胞群显著增加。IL-22+ CD 8 + T细胞频率与AD疾病严重程度相关。我们的数据证实,即使IL-17的表达水平较低,T细胞也可以独立表达IL-22。这证明了T细胞的功能特化,使得“T17”和“T22”T细胞可以驱动炎性皮肤病中表皮病理学的不同特征,包括诱导“T17”T细胞的AMP和“T22”T细胞的表皮增生。考虑到与疾病严重程度的临床相关性,需要进一步表征“T22”T细胞,并且可能具有未来的治疗意义。
Psoriasis and atopic dermatitis (AD) are common inflammatory skin diseases. Up-regulated Th17/IL-23 pathway was demonstrated in psoriasis. Although potential involvement of Th17 T-cells in AD was suggested during acute disease, the role of these cells in chronic AD remains unclear. To examine differences in IL-23/Th17 signal between these diseases and establish relative frequencies of T-cell subsets in AD. Skin biopsies and peripheral blood were collected from chronic AD (n=12) and psoriasis (n=13) patients. Relative frequencies of CD4+ and CD8+ T-cell subsets within these two compartments were examined by intracellular cytokine staining and flow cytometry. In peripheral blood, no significant difference was found in percentages of different T-cell subsets between these diseases. In contrast, psoriatic skin had significantly increased frequencies of Th1 and Th17 T-cells compared with AD, while Th2 T-cells were significantly elevated in AD. Distinct IL-22 producing CD4+ and CD8+ T-cell populations were significantly increased in AD skin, compared to psoriasis. IL-22+CD8+ T-cell frequency correlated with AD disease severity. Our data established that T-cells could independently express IL-22 even with low expression levels of IL-17. This argues for a functional specialization of T-cells such that “T17” and “T22” T-cells may drive different features of epidermal pathology in inflammatory skin diseases, including induction of AMPs for “T17” T-cells and epidermal hyperplasia for “T22” T-cells. Given the clinical correlation with disease severity, further characterization of “T22” T-cells is warranted, and may have future therapeutic implications.
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