IL-36γ Induced by the TLR3-SLUG-VDR Axis Promotes Wound Healing via REG3A
IL-36γ Induced by the TLR3-SLUG-VDR Axis Promotes Wound Healing via REG3A
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TLR3-SLUG-VDR 轴诱导的 IL-36γ 通过 REG3A 促进伤口愈合
DOI：
10.1016/j.jid.2017.07.820
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发表时间：
2017-12-01
影响因子：
6.5
通讯作者：
Lai, Yuping
中科院分区：
文献类型：
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作者：
Jiang, Ziwei;Liu, Yuanqi;Lai, Yuping
IL-36家族成员在过度增殖的角质形成细胞中高度表达，并且在皮肤病如银屑病的发病机制中起重要作用。然而，IL-36细胞因子是否以及如何被诱导以促进伤口愈合仍然未知。在这里，我们发现皮肤损伤增加了IL-36 γ的表达，以促进伤口愈合。从机制上讲，IL-36 γ的表达是由来自受损细胞的RNA通过激活toll样受体3（TLR 3）和含TIR结构域的衔接子诱导IFN-β（TRIF），然后诱导锌指蛋白SLUG以消除维生素D受体（VDR）对IL-36 γ基因启动子的抑制作用而诱导的。IL-36 γ作用于角质形成细胞以诱导REG 3A，其调节角质形成细胞增殖和分化，从而促进伤口再上皮化。这些观察结果表明，皮肤损伤通过TLR 3-SLUG-VDR轴的激活增加IL-36 γ，并且IL-36 γ诱导REG 3A以促进伤口愈合。这些发现还为有助于伤口修复的途径提供了见解。
IL-36 family members are highly expressed in hyperproliferative keratinocytes and play an important role in the pathogenesis of skin diseases such as psoriasis. However, whether and how IL-36 cytokines are induced to promote wound healing remains unknown. Here we showed that skin injury increased the expression of IL-36 gamma to promote wound healing. Mechanistically, the expression of IL-36 gamma was induced by RNAs from damaged cells via the activation of toll-like receptor 3 (TLR3) and TIR-domain-containing adapter-inducing IFN-beta (TRIF) followed by the induction of a zinc finger protein SLUG to abrogate the inhibitory effect of vitamin D receptor (VDR) on the promoter of IL-36 gamma gene. IL-36 gamma acted back on keratinocytes to induce REG3A, which regulated keratinocyte proliferation and differentiation, thus promoting wound re-epithelialization. These observations show that skin injury increases IL-36 gamma via the activation of TLR3-SLUG-VDR axis and that IL-36 gamma induces REG3A to promote wound healing. These findings also provide insights into pathways contributing to wound repair.