An ITAM-Syk-CARD9 signalling axis triggers contact hypersensitivity by stimulating IL-1 production in dendritic cells

Yasukawa, Shinsuke; Miyazaki, Y.; Yoshii, Chika; Nakaya, Masato; Ozaki, Naoko; Toda, Shuji; Kuroda, Etsushi; Ishibashi, Ken; Yasuda, Tomoharu; Natsuaki, Yohei; Mi-ichi, Fumika; Iizasa, Ei’ichi; Nakahara, Takeshi; Yamazaki, Masanori; Kabashima, Kenji; Iwakura, Yoichiro; Takai, Toshiyuki; Saito, Takashi; Kurosaki, Tomohiro; Malissen, Bernard; Ohno, Naohito; Furue, Masutaka; Yoshida, Hiroki; Hara, Hiromitsu

doi:10.1038/ncomms4755

Cited by 66 publications

(55 citation statements)

References 68 publications

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“…in the absence of Mincle was significantly impaired. Mincle uses the Syk/CARD9-signaling pathway, and the pathway in dendritic cells was recently shown to be a crucial signaling axis in induction of the skin CHS response (36). Therefore, endogenous Mincle ligands may serve as auto-adjuvants, activating the innate immune system.…”

Section: Discussionmentioning

confidence: 99%

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

Kostarnoy

Gancheva

Lepenies

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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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.innate immunity | sterile inflammation | allergy | Mincle | cholesterol sulfate

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Section: Discussionmentioning

confidence: 99%

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

Kostarnoy

Gancheva

Lepenies

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…Silica and polycationic particles can interact with plasma membrane phospholipids leading to membrane destabilization and ROS production (3,87). Urate crystals can also bind plasma membrane cholesterol and induce to aggregation of receptors and other molecules within lipid rafts, thus activating Syk-dependent inflammatory signaling and ROS generation (108,176). ROS induction can also be indirect, as for instance in the case of crystalline silica particles that can induce TNF-α production that stimulates ROS generation (12).…”

Section: Ros Production By Nanomaterialsmentioning

confidence: 99%

Oxidative Stress and Inflammation Induced by Environmental and Psychological Stressors: A Biomarker Perspective

Ghezzi

Floridi

Boraschi

et al. 2018

Antioxidants & Redox Signaling

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“…Another signling pathway triggered by contact allergens involves unknown receptors that couple to the kinase Syk [22]. It was shown that the production of IL-1β was mediated by signaling via the kinase Syk coupling to the adaptor CARD9 and Bcl10 for NF-κB activation.…”

Section: The Innate Molecular Immune Response To Contact Allergensmentioning

confidence: 99%

Mechanistic Understanding of Contact Allergy

Martin

2016

Cosmetics

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Cosmetic products contain potential contact allergens or precursors that require metabolic conversion or oxidation to generate contact allergens. The most relevant contact allergens are fragrances and preservatives. These substances can pose hazards to human health due to their ability to activate T cells that can cause allergic contact dermatitis, an inflammatory skin disease. In recent years, much progress has been made in the elucidation of the mechanistic basis for immune system activation by contact allergens. This is essential for the development of better diagnostic tools, targeted therapies and animal-free in vitro assays for contact allergen identification. This overview will highlight some aspects of the activation of innate and adaptive immune responses by contact allergens.

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An ITAM-Syk-CARD9 signalling axis triggers contact hypersensitivity by stimulating IL-1 production in dendritic cells

Cited by 66 publications

References 68 publications

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

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

Oxidative Stress and Inflammation Induced by Environmental and Psychological Stressors: A Biomarker Perspective

Mechanistic Understanding of Contact Allergy

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