Immunomodulatory leptin receptor + sympathetic perineurial barrier cells protect against obesity by facilitating brown adipose tissue thermogenesis.

Autor:	Haberman ER; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK., Sarker G; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK., Arús BA; Instituto Gulbenkian de Ciência, Oeiras, Portugal; Helmholtz-Zentrum Dresden - Rossendorf (HZDR), Dresden, Germany., Ziegler KA; Institute of Pharmacology and Toxicology, Technical University Munich (TUM), Munich, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany., Meunier S; Institute of Pharmacology and Toxicology, Technical University Munich (TUM), Munich, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany., Martínez-Sánchez N; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK; Instituto Gulbenkian de Ciência, Oeiras, Portugal., Freibergerová E; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK., Yilmaz-Özcan S; Instituto Gulbenkian de Ciência, Oeiras, Portugal., Fernández-González I; Neurobesity Group, Department of Physiology, Center for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela, Santiago, Spain., Zentai C; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK., O'Brien CJO; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK., Grainger DE; Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK., Sidarta-Oliveira D; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK., Chakarov S; Singapore Immunology Network (SIgN), A(∗)STAR, Singapore, Singapore; Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China., Raimondi A; Vita-Salute San Raffaele University, Milan, Italy., Iannacone M; Vita-Salute San Raffaele University, Milan, Italy; Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy., Engelhardt S; Institute of Pharmacology and Toxicology, Technical University Munich (TUM), Munich, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany., López M; Neurobesity Group, Department of Physiology, Center for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela, Santiago, Spain., Ginhoux F; Singapore Immunology Network (SIgN), A(∗)STAR, Singapore, Singapore; Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China., Domingos AI; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK. Electronic address: ana.domingos@dpag.ox.ac.uk.
Jazyk:	angličtina
Zdroj:	Immunity [Immunity] 2024 Jan 09; Vol. 57 (1), pp. 141-152.e5. Date of Electronic Publication: 2023 Dec 12.
DOI:	10.1016/j.immuni.2023.11.006
Abstrakt:	Adipose tissues (ATs) are innervated by sympathetic nerves, which drive reduction of fat mass via lipolysis and thermogenesis. Here, we report a population of immunomodulatory leptin receptor-positive (LepR + ) sympathetic perineurial barrier cells (SPCs) present in mice and humans, which uniquely co-express Lepr and interleukin-33 (Il33) and ensheath AT sympathetic axon bundles. Brown ATs (BATs) of mice lacking IL-33 in SPCs (SPC ΔIl33 ) had fewer regulatory T (Treg) cells and eosinophils, resulting in increased BAT inflammation. SPC ΔIl33 mice were more susceptible to diet-induced obesity, independently of food intake. Furthermore, SPC ΔIl33 mice had impaired adaptive thermogenesis and were unresponsive to leptin-induced rescue of metabolic adaptation. We therefore identify LepR + SPCs as a source of IL-33, which orchestrate an anti-inflammatory BAT environment, preserving sympathetic-mediated thermogenesis and body weight homeostasis. LepR + IL-33 + SPCs provide a cellular link between leptin and immune regulation of body weight, unifying neuroendocrinology and immunometabolism as previously disconnected fields of obesity research. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2023. Published by Elsevier Inc.)
Databáze:	MEDLINE
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