Details

Autor(en) / Beteiligte

• Kostarnoy, Alexey V.
• Gancheva, Petya G.
• Lepenies, Bernd
• Tukhvatulin, Amir I.
• Dzharullaeva, Alina S.
• Polyakov, Nikita B.
• Grumov, Daniil A.
• Egorova, Daria A.
• Kulibin, Andrey Y.
• Bobrov, Maxim A.
• Malolina, Ekaterina A.
• Zykin, Pavel A.
• Soloviev, Andrey I.
• Riabenko, Evgeniy
• Maltseva, Diana V.
• Sakharov, Dmitry A.
• Tonevitsky, Alexander G.
• Verkhovskaya, Lyudmila V.
• Logunov, Denis Y.
• Naroditsky, Boris S.
• Gintsburg, Alexander L.

Titel

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

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2017-03, Vol.114 (13), p.E2758-E2765

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2017

Quelle

EZB Free E-Journals

Beschreibungen/Notizen

• 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.