皮肤中产生白介素-17 的 γδ T 细胞在皮肤炎症中起关键作用。
Pivotal role of dermal IL-17-producing γδ T cells in skin inflammation.
机构信息
Department of Dermatology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 20025, PR China.
出版信息
Immunity. 2011 Oct 28;35(4):596-610. doi: 10.1016/j.immuni.2011.08.001. Epub 2011 Oct 6.
Interleukin-23 (IL-23) and CD4(+) T helper 17 (Th17) cells are thought to be critical in psoriasis pathogenesis. Here, we report that IL-23 predominantly stimulated dermal γδ T cells to produce IL-17 that led to disease progression. Dermal γδ T cells constitutively expressed the IL-23 receptor (IL-23R) and transcriptional factor RORγt. IL-17 production from dermal γδ T cells was independent of αβ T cells. The epidermal hyperplasia and inflammation induced by IL-23 were significantly decreased in T cell receptor δ-deficient (Tcrd(-/-)) and IL-17 receptor-deficient (Il17ra(-/-)) mice but occurred normally in Tcra(-/-) mice. Imiquimod-induced skin pathology was also significantly decreased in Tcrd(-/-) mice. Perhaps further promoting disease progression, IL-23 stimulated dermal γδ T cell expansion. In psoriasis patients, γδ T cells were greatly increased in affected skin and produced large amounts of IL-17. Thus, IL-23-responsive dermal γδ T cells are the major IL-17 producers in the skin and may represent a novel target for the treatment of psoriasis.
白细胞介素-23（IL-23）和 CD4+辅助性 T 细胞 17（Th17）细胞被认为在银屑病发病机制中起关键作用。在这里，我们报告说，IL-23 主要刺激皮肤 γδ T 细胞产生 IL-17，导致疾病进展。皮肤 γδ T 细胞持续表达 IL-23 受体（IL-23R）和转录因子 RORγt。皮肤 γδ T 细胞产生的 IL-17 不依赖于 αβ T 细胞。在 T 细胞受体 δ 缺陷（Tcrd(-/-)）和白细胞介素 17 受体缺陷（Il17ra(-/-)）小鼠中，IL-23 诱导的表皮过度增生和炎症显著减少，但在 Tcra(-/-)小鼠中则正常发生。TCRd(-/-)小鼠的咪喹莫特诱导的皮肤病理也显著减少。也许进一步促进疾病进展，IL-23 刺激皮肤 γδ T 细胞扩增。在银屑病患者中，受影响皮肤中的 γδ T 细胞大量增加，并产生大量的 IL-17。因此，IL-23 反应性皮肤 γδ T 细胞是皮肤中主要的 IL-17 产生细胞，可能是治疗银屑病的新靶点。
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