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  • 标题:Receptor Mincle promotes skin allergies and is capable of recognizing cholesterol sulfate
  • 本地全文:下载
  • 作者:Alexey V. Kostarnoy ; Petya G. Gancheva ; Bernd Lepenies
  • 期刊名称:Proceedings of the National Academy of Sciences
  • 印刷版ISSN:0027-8424
  • 电子版ISSN:1091-6490
  • 出版年度:2017
  • 卷号:114
  • 期号:13
  • 页码:E2758-E2765
  • DOI:10.1073/pnas.1611665114
  • 语种:English
  • 出版社:The National Academy of Sciences of the United States of America
  • 摘要:Sterile (noninfected) inflammation underlies the pathogenesis of many widespread diseases, such as allergies and autoimmune diseases. The evolutionarily conserved innate immune system is considered to play a key role in tissue injury recognition and the subsequent development of sterile inflammation; however, the underlying molecular mechanisms are not yet completely understood. Here, we show that cholesterol sulfate, a molecule present in relatively high concentrations in the epithelial layer of barrier tissues, is selectively recognized by Mincle (Clec4e), a C-type lectin receptor of the innate immune system that is strongly up-regulated in response to skin damage. Mincle activation by cholesterol sulfate causes the secretion of a range of proinflammatory mediators, and s.c. injection of cholesterol sulfate results in a Mincle-mediated induction of a severe local inflammatory response. In addition, our study reveals a role of Mincle as a driving component in the pathogenesis of allergic skin inflammation. In a well-established model of allergic contact dermatitis, the absence of Mincle leads to a significant suppression of the magnitude of the skin inflammatory response as assessed by changes in ear thickness, myeloid cell infiltration, and cytokine and chemokine secretion. Taken together, our results provide a deeper understanding of the fundamental mechanisms underlying sterile inflammation.
  • 关键词:innate immunity ; sterile inflammation ; allergy ; Mincle ; cholesterol sulfate
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