Interleukin-22, a TH17 cytokine, mediates IL-23-induced dermal inflammation and acanthosis
Interleukin-22, a TH17 cytokine, mediates IL-23-induced dermal inflammation and acanthosis
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DOI：
10.1038/nature05505
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发表时间：
2007-02-08
期刊：
影响因子：
64.8
通讯作者：
Ouyang, Wenjun
中科院分区：
文献类型：
--
作者：
Zheng, Yan;Danilenko, Dimitry M.;Ouyang, Wenjun
银屑病是一种慢性炎症性皮肤病，其特征为表皮增生（棘皮病）、白细胞浸润真皮和表皮以及血管扩张和生长（1）。牛皮癣的病因是什么？牛皮癣的病因是什么？最近，发现白细胞介素（IL）-2,3，一种参与产生IL-17的T辅助细胞（T（H）17细胞）发育的细胞因子（2，3），在银屑病发病机制中具有潜在功能（4，5）。在这里，我们表明，IL-22优先产生的T（H）17细胞和介导的棘层由IL-23诱导。我们发现IL-23或IL-6可以直接诱导小鼠和人幼稚T细胞产生IL-22。然而，从T（H）17细胞产生IL-22和IL-17受到差异调节。转化生长因子-β虽然对IL-17的产生至关重要，但实际上抑制IL-22的产生。此外，IL-22在体内通过激活Stat 3（信号转导和转录激活因子3）介导IL-23诱导的棘皮症和皮肤炎症。我们的研究结果表明，T（H）17细胞，通过产生IL-22和IL-17，可能在宿主防御和自身免疫性疾病，如银屑病的发病机制中具有重要的功能。IL-22作为T细胞产生的效应细胞因子，介导免疫系统和上皮细胞之间的串扰。
Psoriasis is a chronic inflammatory skin disease characterized by hyperplasia of the epidermis ( acanthosis), infiltration of leukocytes into both the dermis and epidermis, and dilation and growth of blood vessels(1). The underlying cause of the epidermal acanthosis in psoriasis is still largely unknown. Recently, interleukin (IL)-23, a cytokine involved in the development of IL-17-producing T helper cells (T(H)17 cells)(2,3), was found to have a potential function in the pathogenesis of psoriasis(4,5). Here we show that IL-22 is preferentially produced by T(H)17 cells and mediates the acanthosis induced by IL-23. We found that IL-23 or IL-6 can directly induce the production of IL-22 from both murine and human naive T cells. However, the production of IL-22 and IL-17 from T(H)17 cells is differentially regulated. Transforming growth factor-beta, although crucial for IL-17 production, actually inhibits IL-22 production. Furthermore, IL-22 mediates IL-23-induced acanthosis and dermal inflammation through the activation of Stat3 ( signal transduction and activators of transcription 3) in vivo. Our results suggest that T(H)17 cells, through the production of both IL-22 and IL-17, might have essential functions in host defence and in the pathogenesis of autoimmune diseases such as psoriasis. IL-22, as an effector cytokine produced by T cells, mediates the crosstalk between the immune system and epithelial cells.