Induction of IL-17+ T cell trafficking and development by IFN-gamma: mechanism and pathological relevance in psoriasis.
Induction of IL-17+ T cell trafficking and development by IFN-gamma: mechanism and pathological relevance in psoriasis.
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DOI：
10.4049/jimmunol.181.7.4733
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发表时间：
2008-10-01
期刊：
影响因子：
--
通讯作者：
Zou W
中科院分区：
文献类型：
--
作者：
Kryczek I;Bruce AT;Gudjonsson JE;Johnston A;Aphale A;Vatan L;Szeliga W;Wang Y;Liu Y;Welling TH;Elder JT;Zou W
Th 1和Th 17 T细胞通常共同定位于病理环境中，然而Th 1衍生的干扰素（IFN）-γ在体外抑制Th 17细胞的发育。我们探索了人类这种矛盾的生理基础。在这里，我们证明了银屑病皮损中CD 4 +IL-17+和CD 8 +IL-17+ T细胞数量的增加。此外，我们表明，髓样抗原呈递细胞（APC）有力地支持IL-17+ T细胞的诱导，并且这种活性在银屑病中大大增加。我们测试了可能解释这种活动的刺激。银屑病患者外周血和皮损中Th 1细胞和IFN-γ水平均升高。我们表明IFN-γ通过IL-1和IL-23编程骨髓APC诱导人IL-17+ T细胞。IFN-γ还刺激CCL 20的APC产生，支持IL-17+ T细胞的迁移，并与IL-17协同产生β-防御素2（HBD-2），这是一种由银屑病角质形成细胞高度过表达的抗微生物和趋化蛋白。这项研究揭示了Th 1和IL-17+ T细胞之间的一种新的机制相互作用，挑战了Th 1细胞通过IFN-γ抑制Th 17发育的观点，并表明Th 1和IL-17+ T细胞可能协同促进人类自身免疫性疾病。
Th1 and Th17 T cells are often co-localized in pathological environments, yet Th1 derived-interferon (IFN)-γ inhibits Th17 cell development in vitro. We explored the physiologic basis of this paradox in humans. Here we demonstrate increased numbers of CD4+IL-17+ and CD8+IL-17+ T cells in skin lesions of psoriasis. Furthermore, we show that myeloid antigen presenting cells (APCs) potently support induction of IL-17+ T cells, and that this activity is greatly increased in psoriasis. We tested stimuli which might account for this activity. Th1 cells and IFN-γ are increased in psoriatic blood and lesional skin. We show that IFN-γ programs myeloid APCs to induce human IL-17+ T cells via IL-1 and IL-23. IFN-γ also stimulates APC production of CCL20, supporting migration of IL-17+ T cells, and synergizes with IL-17 in the production of β-defensin 2 (HBD-2), an antimicrobial and chemotactic protein highly overexpressed by psoriatic keratinocytes. This study reveals a novel mechanistic interaction between Th1 and IL-17+ T cells, challenges the view that Th1 cells suppress Th17 development through IFN-γ, and suggests that Th1 and IL-17+ T cells may collaboratively contribute to human autoimmune diseases.
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