Receptor Mincle promotes skin allergies and is capable of recognizing cholesterol sulfate.

Autor: Kostarnoy AV; Laboratory of Immunobiotechnology, N. F. Gamaleya Federal Research Center of Epidemiology and Microbiology, 123098 Moscow, Russia; kostarnoy@yandex.ru., Gancheva PG; Laboratory of Immunobiotechnology, N. F. Gamaleya Federal Research Center of Epidemiology and Microbiology, 123098 Moscow, Russia., Lepenies B; Immunology Unit, Research Center for Emerging Infections and Zoonoses, University of Veterinary Medicine, 30559 Hannover, Germany., Tukhvatulin AI; Laboratory of Cellular Microbiology, N. F. Gamaleya Federal Research Center of Epidemiology and Microbiology, 123098 Moscow, Russia., Dzharullaeva AS; Laboratory of Cellular Microbiology, N. F. Gamaleya Federal Research Center of Epidemiology and Microbiology, 123098 Moscow, Russia., Polyakov NB; Laboratory of Detection and Ultrastructural Analysis of Microorganisms, N. F. Gamaleya Federal Research Center of Epidemiology and Microbiology, 123098 Moscow, Russia.; Laboratory of Instrumental Methods and Organic Reagents, Vernadsky Institute of Geochemistry and Analytical Chemistry, Russian Academy of Sciences, 119991 Moscow, Russia., Grumov DA; Laboratory of Detection and Ultrastructural Analysis of Microorganisms, N. F. Gamaleya Federal Research Center of Epidemiology and Microbiology, 123098 Moscow, Russia., Egorova DA; Laboratory of Immunobiotechnology, N. F. Gamaleya Federal Research Center of Epidemiology and Microbiology, 123098 Moscow, Russia., Kulibin AY; Laboratory of Evolutionary Developmental Biology, Koltzov Institute of Developmental Biology, Russian Academy of Sciences, 119071 Moscow, Russia., Bobrov MA; Department of Pathology, M. F. Vladimirsky Moscow Regional Clinical Research Institute, 129110 Moscow, Russia., Malolina EA; Laboratory of Evolutionary Developmental Biology, Koltzov Institute of Developmental Biology, Russian Academy of Sciences, 119071 Moscow, Russia.; Laboratory of Cell Engineering, Ivanovsky Institute of Virology, N. F. Gamaleya Federal Research Center of Epidemiology and Microbiology, 123098 Moscow, Russia., Zykin PA; Department of Cytology and Histology, St. Petersburg State University, 199034 St. Petersburg, Russia., Soloviev AI; Laboratory of Detection and Ultrastructural Analysis of Microorganisms, N. F. Gamaleya Federal Research Center of Epidemiology and Microbiology, 123098 Moscow, Russia., Riabenko E; Department of Control and Applied Mathematics, Moscow Institute of Physics and Technology, 141700 Dolgoprudny, Russia.; Faculty of Computer Science, Big Data and Information Retrieval School, National Research University Higher School of Economics, Moscow 101000, Russia., Maltseva DV; Scientific Research Centre Bioclinicum, 115088 Moscow, Russia., Sakharov DA; Scientific Research Centre Bioclinicum, 115088 Moscow, Russia., Tonevitsky AG; Department of Translational Oncology, P. Hertsen Moscow Oncology Research Institute, National Center of Medical Radiological Research, Moscow 125284, Russia., Verkhovskaya LV; Laboratory of Molecular Biotechnology, N. F. Gamaleya Federal Research Center of Epidemiology and Microbiology, 123098 Moscow, Russia., Logunov DY; Laboratory of Cellular Microbiology, N. F. Gamaleya Federal Research Center of Epidemiology and Microbiology, 123098 Moscow, Russia., Naroditsky BS; Laboratory of Immunobiotechnology, N. F. Gamaleya Federal Research Center of Epidemiology and Microbiology, 123098 Moscow, Russia., Gintsburg AL; Laboratory of Gene Engineering of Pathogenic Microorganisms, N. F. Gamaleya Federal Research Center of Epidemiology and Microbiology, 123098 Moscow, Russia.
Jazyk: angličtina
Zdroj: Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2017 Mar 28; Vol. 114 (13), pp. E2758-E2765. Date of Electronic Publication: 2017 Mar 14.
DOI: 10.1073/pnas.1611665114
Abstrakt: 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.
Databáze: MEDLINE
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