Molecular Immunology, Department of Allergy and Clinical Immunology, National Heart and Lung Institute, Imperial College, London, United Kingdom.
J Clin Invest. 2009 Dec;119(12):3573-85. doi: 10.1172/JCI40202. Epub 2009 Nov 16.
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.
Th 亚群根据其产生的谱系指示细胞因子和功能来定义。在这项研究中，我们鉴定了一组人 Th 细胞，它们浸润在患有炎症性皮肤病的个体的表皮中，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。从银屑病患者中分离出来的 Th22 克隆在培养中稳定，并表现出与 Th1、Th2 和 Th17 细胞明显不同的转录组特征；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一个转录组反应谱，其中包括参与先天免疫途径以及适应性免疫的诱导和调节的基因。这些促炎 Th22 反应协同依赖于 IL-22 和 TNF-α。此外，Th22 上清液增强了体外损伤模型中的伤口愈合，这完全依赖于 IL-22。总之，人 Th22 亚群可能代表一个具有独特身份的独立 T 细胞亚群，在炎症性皮肤病的表皮层中存在。针对 Th22 亚群的未来策略可能对慢性炎症性皮肤病有价值。
