IL-36 signaling in keratinocytes controls early IL-23 production in psoriasis-like dermatitis
IL-36 signaling in keratinocytes controls early IL-23 production in psoriasis-like dermatitis
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DOI：
10.26508/lsa.202000688
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发表时间：
2020-06-01
影响因子：
4.4
通讯作者：
Gabay, Cem
中科院分区：
文献类型：
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作者：
Goldstein, Jeremie D.;Bassoy, Esen Y.;Gabay, Cem
IL-36 R信号通路在银屑病发病机制中起重要作用。我们应该评估角质形成细胞中IL-36 R在Aldara诱导的银屑病样皮炎病理学中的特异性功能。角质形成细胞中IL-36 R缺失的Il 36 r（Delta K）小鼠对Aldara诱导的耳部炎症的抗性与Il 36 r（-/-）小鼠相似，但棘皮症仅在Il 36 r（-/-）小鼠中得到预防。FACS分析显示，角质形成细胞中的IL-36 R信号传导对于Aldara治疗耳中的早期中性粒细胞浸润是必需的。RNASeq和qRT-PCR实验证明了IL-36 R信号传导在角质形成细胞中在早期时间点诱导IL-23、IL-17和IL-22的关键作用。综上所述，我们的结果表明，角质形成细胞中的IL-36 R信号传导通过触发IL-23/IL-17/IL-22细胞因子的早期产生和中性粒细胞浸润在诱导Aldara诱导的银屑病样皮炎中起主要作用。
IL-36R signaling plays an important role in the pathogenesis of psoriasis. We ought to assess the specific function of IL-36R in keratinocytes for the pathology of Aldara-induced psoriasis-like dermatitis. Il36r(Delta K) mice presenting deletion of IL-36R in keratinocytes were similarly resistant to Aldara-induced ear inflammation as Il36r(-/-) mice, but acanthosis was only prevented in Il36r(-/-) mice. FACS analysis revealed that IL-36R signaling in keratinocytes is mandatory for early neutrophil infiltration in Aldara-treated ears. RNASeq and qRT-PCR experiments demonstrated the crucial role of IL-36R signaling in keratinocytes for induction of IL-23, IL-17, and IL-22 at earlytime points. Taken together, our results demonstrate that IL-36R signaling in keratinocytes plays a major role in the induction of Aldara-induced psoriasis-like dermatitis by triggering early production of IL-23/IL-17/IL-22 cytokines and neutrophil infiltration.