Lipid-orchestrated paracrine circuit coordinates mast cell maturation and anaphylaxis through functional interaction with fibroblasts.

Autor: Taketomi Y; Laboratory of Microenvironmental and Metabolic Health Sciences, Center for Disease Biology and Integrative Medicine, The University of Tokyo, Tokyo 113-8655, Japan; Lipid Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan., Higashi T; Laboratory of Microenvironmental and Metabolic Health Sciences, Center for Disease Biology and Integrative Medicine, The University of Tokyo, Tokyo 113-8655, Japan., Kano K; Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-8655, Japan., Miki Y; Laboratory of Microenvironmental and Metabolic Health Sciences, Center for Disease Biology and Integrative Medicine, The University of Tokyo, Tokyo 113-8655, Japan., Mochizuki C; Laboratory of Microenvironmental and Metabolic Health Sciences, Center for Disease Biology and Integrative Medicine, The University of Tokyo, Tokyo 113-8655, Japan., Toyoshima S; Allergy and Immunology Research Project Team, Research Institute of Medical Science, Center for Allergy, and Division of Internal Medicine, Department of Respiratory Medicine, Nihon University School of Medicine, Tokyo 173-8610, Japan; Department of Biochemistry & Molecular Biology, Nippon Medical School, Tokyo 113-8602, Japan., Okayama Y; Allergy and Immunology Research Project Team, Research Institute of Medical Science, Center for Allergy, and Division of Internal Medicine, Department of Respiratory Medicine, Nihon University School of Medicine, Tokyo 173-8610, Japan; Department of Allergy and Internal Medicine, Misato Kenwa Hospital, Saitama 341-8555, Japan; Department of Internal Medicine, Division of Respiratory Medicine, Showa University School of Medicine, Tokyo 142-8666, Japan; Advanced Medical Science Research Center, Gunma Paz University Graduate School of Health Sciences, Takasaki 370-0006, Japan., Nishito Y; Center for Basic Technology Research, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan., Nakae S; Graduate School of Integrated Sciences for Life, Hiroshima University, Hiroshima 739-8528, Japan., Tanaka S; Department of Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan., Tokuoka SM; Department of Lipidomics, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan., Oda Y; Department of Lipidomics, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan., Shichino S; Division of Molecular Regulation of Inflammatory and Immune Diseases, Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba 278-0022, Japan., Ueha S; Division of Molecular Regulation of Inflammatory and Immune Diseases, Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba 278-0022, Japan., Matsushima K; Division of Molecular Regulation of Inflammatory and Immune Diseases, Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba 278-0022, Japan., Akahoshi N; Department of Immunology, Akita University Graduate School of Medicine, Akita 010-8543, Japan., Ishii S; Department of Immunology, Akita University Graduate School of Medicine, Akita 010-8543, Japan., Chun J; Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA., Aoki J; Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-8655, Japan., Murakami M; Laboratory of Microenvironmental and Metabolic Health Sciences, Center for Disease Biology and Integrative Medicine, The University of Tokyo, Tokyo 113-8655, Japan; Lipid Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan; AMED-CREST, Japan Agency for Medical Research and Development, Tokyo 100-0004, Japan. Electronic address: makmurak@m.u-tokyo.ac.jp.
Jazyk: angličtina
Zdroj: Immunity [Immunity] 2024 Aug 13; Vol. 57 (8), pp. 1828-1847.e11. Date of Electronic Publication: 2024 Jul 12.
DOI: 10.1016/j.immuni.2024.06.012
Abstrakt: Interaction of mast cells (MCs) with fibroblasts is essential for MC maturation within tissue microenvironments, although the underlying mechanism is incompletely understood. Through a phenotypic screening of >30 mouse lines deficient in lipid-related genes, we found that deletion of the lysophosphatidic acid (LPA) receptor LPA 1 , like that of the phospholipase PLA2G3, the prostaglandin D 2 (PGD 2 ) synthase L-PGDS, or the PGD 2 receptor DP1, impairs MC maturation and thereby anaphylaxis. Mechanistically, MC-secreted PLA2G3 acts on extracellular vesicles (EVs) to supply lysophospholipids, which are converted by fibroblast-derived autotaxin (ATX) to LPA. Fibroblast LPA 1 then integrates multiple pathways required for MC maturation by facilitating integrin-mediated MC-fibroblast adhesion, IL-33-ST2 signaling, L-PGDS-driven PGD 2 generation, and feedforward ATX-LPA 1 amplification. Defective MC maturation resulting from PLA2G3 deficiency is restored by supplementation with LPA 1 agonists or PLA2G3-modified EVs. Thus, the lipid-orchestrated paracrine circuit involving PLA2G3-driven lysophospholipid, eicosanoid, integrin, and cytokine signaling fine-tunes MC-fibroblast communication, ensuring MC maturation.
Competing Interests: Declaration of interests J.C. has an employment relationship with Neurocrine Biosciences, Inc. as a Distinguished Scholar, unrelated to the current manuscript.
(Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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