气候变化领域集成服务门户(CCPortal): The CysLT2R receptor mediates leukotriene C4-driven acute and chronic itch

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DOI	10.1073/pnas.2022087118
	The CysLT2R receptor mediates leukotriene C4-driven acute and chronic itch
	Voisin T.; Perner C.; Messou M.-A.; Shiers S.; Ualiyeva S.; Kanaoka Y.; Price T.J.; Sokol C.L.; Bankova L.G.; Frank Austen K.; Chiu I.M.
发表日期	2021
ISSN	00278424
卷号	118 期号:13
英文摘要	Acute and chronic itch are burdensome manifestations of skin pathologies including allergic skin diseases and atopic dermatitis, but the underlying molecular mechanisms are not well understood. Cysteinyl leukotrienes (CysLTs), comprising LTC4, LTD4, and LTE4, are produced by immune cells during type 2 inflammation. Here, we uncover a role for LTC4 and its signaling through the CysLT receptor 2 (CysLT2R) in itch. Cysltr2 transcript is highly expressed in dorsal root ganglia (DRG) neurons linked to itch in mice. We also detected CYSLTR2 in a broad population of human DRG neurons. Injection of leukotriene C4 (LTC4) or its nonhydrolyzable form NMLTC4, but neither LTD4 nor LTE4, induced dose-dependent itch but not pain behaviors in mice. LTC4-mediated itch differed in bout duration and kinetics from pruritogens histamine, compound 48/80, and chloroquine. NMLTC4-induced itch was abrogated in mice deficient for Cysltr2 or when deficiency was restricted to radioresistant cells. Itch was unaffected in mice deficient for Cysltr1, Trpv1, or mast cells (WSh mice). CysLT2R played a role in itch in the MC903 mouse model of chronic itch and dermatitis, but not in models of dry skin or compound 48/80- or Alternaria-induced itch. In MC903-treated mice, CysLT levels increased in skin over time, and Cysltr2−/− mice showed decreased itch in the chronic phase of inflammation. Collectively, our study reveals that LTC4 acts through CysLT2R as its physiological receptor to induce itch, and CysLT2R contributes to itch in a model of dermatitis. Therefore, targeting CysLT signaling may be a promising approach to treat inflammatory itch. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Atopic dermatitis; Inflammation; Itch; Neuroimmune; Skin
语种	英语
scopus关键词	chloroquine; compound 48-80; cysteinyl leukotriene 2 receptor; histamine; leukotriene C4; leukotriene D4; peptidoleukotriene; unclassified drug; Alternaria; animal cell; animal experiment; animal tissue; Article; cell damage; controlled study; Cysltr1 gene; Cysltr2 gene; dermatitis; disease association; disease duration; dose response; dry skin; female; ganglion; gene; gene expression; gene function; gene identification; genetic damage; genetic transcription; human; human tissue; kinetics; male; mast cell; mouse; nonhuman; physiological process; priority journal; protein targeting; pruritus; radioresistant cell line; signal transduction; Trpv1 gene
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180077
作者单位	Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, United States; Center for Immunology & Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, United States; Center for Advanced Pain Studies, School of Behavioral and Brain Sciences, University of Texas at Dallas, Dallas, TX 75080, United States; Division of Allergy and Clinical Immunology, Jeff and Penny Vinik Center for Allergic Disease Research, Brigham & Women’s Hospital, Boston, MA 02115, United States; Department of Medicine, Harvard Medical School, Boston, MA 02115, United States
推荐引用方式 GB/T 7714	Voisin T.,Perner C.,Messou M.-A.,et al. The CysLT2R receptor mediates leukotriene C4-driven acute and chronic itch[J],2021,118(13).
APA	Voisin T..,Perner C..,Messou M.-A..,Shiers S..,Ualiyeva S..,...&Chiu I.M..(2021).The CysLT2R receptor mediates leukotriene C4-driven acute and chronic itch.Proceedings of the National Academy of Sciences of the United States of America,118(13).
MLA	Voisin T.,et al."The CysLT2R receptor mediates leukotriene C4-driven acute and chronic itch".Proceedings of the National Academy of Sciences of the United States of America 118.13(2021).