Th22 cells represent a distinct human T cell subset involved in epidermal immunity and remodeling
Th22 cells represent a distinct human T cell subset involved in epidermal immunity and remodeling
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DOI：
10.1172/jci40202
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发表时间：
2009-12-01
影响因子：
15.9
通讯作者：
Cavani, Andrea
中科院分区：
文献类型：
--
作者：
Eyerich, Stefanie;Eyerich, Kilian;Cavani, Andrea
这些亚群是根据它们产生的指示谱系的细胞因子和功能来定义的。在这项研究中，我们已经确定了人类Th细胞的一个亚群，它浸润在炎症性皮肤疾病患者的表皮，其特征是分泌IL-22和tnf - α，但不分泌ifn - γ、IL-4或IL-17。与Th17亚群类似，具有这种细胞因子特征的细胞被命名为Th22亚群。来自牛皮癣患者的Th22克隆在培养中是稳定的，并且表现出与Th1、Th2和Th17细胞明显分离的转录组谱；它包括编码参与组织重塑的蛋白质的基因，如FGFs，以及参与血管生成和纤维化的趋化因子。暴露于Th22上清液的原代人角质形成细胞表达了转录组反应谱，其中包括参与先天免疫途径和诱导和调节适应性免疫的基因。这些促炎Th22反应协同依赖于IL-22和tnf - α。此外，在完全依赖IL-22的体外损伤模型中，Th22上清液促进了伤口愈合。总之，人类Th22亚群可能代表一个独立的T细胞亚群，在基因表达和功能方面具有独特的身份，存在于炎症性皮肤病的表皮层中。未来针对Th22亚群的策略可能对慢性炎症性皮肤病有价值。
Th subsets are defined according to their production of lineage-indicating cytokines and functions. In this study, we have identified a subset of human Th cells that infiltrates the epidermis in individuals with inflammatory skin disorders and is characterized by the secretion of IL-22 and TNF-alpha, but not IFN-gamma, IL-4, or IL-17. In analogy to the Th17 subset, cells with this cytokine profile have been named the Th22 subset. Th22 clones derived from patients with psoriasis were stable in culture and exhibited a transcriptome profile clearly separate from those of Th1, Th2, and Th17 cells; it included genes encoding proteins involved in tissue remodeling, such as FGFs, and chemokines involved in angiogenesis and fibrosis. Primary human keratinocytes exposed to Th22 supernatants expressed a transcriptome response profile that included genes involved in innate immune pathways and the induction and modulation of adaptive immunity. These proinflammatory Th22 responses were synergistically dependent on IL-22 and TNF-alpha. Furthermore, Th22 supernatants enhanced wound healing in an in vitro injury model, which was exclusively dependent on IL-22. In conclusion, the human Th22 subset may represent a separate T cell subset with a distinct identity with respect to gene expression and function, present within the epidermal layer in inflammatory skin diseases. Future strategies directed against the Th22 subset may be of value in chronic inflammatory skin disorders.