title: Activated type 2 innate lymphoid cells regulate beige fat biogenesis.
abstract: Type 2 innate lymphoid cells (ILC2s), an innate source of the type 2 cytokines interleukin (IL)-5 and -13, participate in the maintenance of tissue homeostasis. Although type 2 immunity is critically important for mediating metabolic adaptations to environmental cold, the functions of ILC2s in beige or brown fat development are poorly defined. We report here that activation of ILC2s by IL-33 is sufficient to promote the growth of functional beige fat in thermoneutral mice. Mechanistically, ILC2 activation results in the proliferation of bipotential adipocyte precursors (APs) and their subsequent commitment to the beige fat lineage. Loss- and gain-of-function studies reveal that ILC2- and eosinophil-derived type 2 cytokines stimulate signaling via the IL-4Rα in PDGFRα(+) APs to promote beige fat biogenesis. Together, our results highlight a critical role for ILC2s and type 2 cytokines in the regulation of adipocyte precursor numbers and fate, and as a consequence, adipose tissue homeostasis. PAPERCLIP:
authors.affiliation: Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA 94158-9001, USA.
authors.forename: Min-Woo
authors.initials: MW
authors.lastname: Lee
authors.affiliation: Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA 94158-9001, USA.
authors.forename: Justin I
authors.initials: JI
authors.lastname: Odegaard
authors.affiliation: Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA 94158-9001, USA.
authors.forename: Lata
authors.initials: L
authors.lastname: Mukundan
authors.affiliation: Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA 94158-9001, USA.
authors.forename: Yifu
authors.initials: Y
authors.lastname: Qiu
authors.affiliation: Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA 94143-0795, USA.
authors.forename: Ari B
authors.initials: AB
authors.lastname: Molofsky
authors.affiliation: Department of Medicine, University of California, San Francisco, CA 94143-0795, USA.
authors.forename: Jesse C
authors.initials: JC
authors.lastname: Nussbaum
authors.affiliation: Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA 94158-9001, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Yun
authors.affiliation: Department of Medicine, University of California, San Francisco, CA 94143-0795, USA; Department of Microbiology and Immunology, University of California, San Francisco, CA 94143-0795, USA; Howard Hughes Medical Institute, University of California, San Francisco, CA 94143-0795, USA.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Locksley
authors.affiliation: Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA 94158-9001, USA; Departments of Physiology and Medicine, University of California San Francisco, San Francisco, CA 94158-9001, USA. Electronic address: ajay.chawla@ucsf.edu.
authors.forename: Ajay
authors.initials: A
authors.lastname: Chawla
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000818:Animals; D049109:Cell Proliferation; D005260:Female; D018793:Interleukin-13 / Q000378:metabolism; D000067596:Interleukin-33; D007378:Interleukins / Q000276:immunology; D008214:Lymphocytes / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism; D019948:Receptors, Interleukin-4 / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism
chemical_list: C506535:Il33 protein, mouse; D018793:Interleukin-13; D000067596:Interleukin-33; D007378:Interleukins; D019948:Receptors, Interleukin-4; D020796:Receptor, Platelet-Derived Growth Factor alpha