Activated Type 2 Innate Lymphoid Cells Regulate Beige Fat Biogenesis

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. [Display omitted] [Display omitted] •IL-33 activates ILC2s to stimulate biogenesis of thermogenic beige fat•Activated ILC2s promote proliferation and commitment of adipocyte precursors•IL-4 and IL-13 control the physiologic expansion of beige adipocyte precursors•Signaling via IL-4Rα in adipocyte progenitors controls beige fat biogenesis Activation of type 2 innate lymphoid cells (ILCs) and type 2 immunity directly promote the proliferation of adipocyte precursors and their subsequent commitment to the beige fat lineage, revealing a role for ILCs in thermal homeostasis.