Fig. 3. Immune regulation of thermogenesis.

Upon cold exposure, M2 macrophages promote the differentiation of beige adipocytes from PDGFRα+ stromal cells. This process is mediated by IL-4 produced by eosinophils. IL-4 and IL-13 derived from eosinophils and ILC2s also promote the proliferation of PDGFRα+ cells to facilitate beiging. While the mechanism by which M2 macrophages promote beiging is unclear, ILC2s and NKT cells promote the upregulation of UCP-1 and FGF-21 in adipose tissue, respectively. Innervation mediated by γδT cell-derived IL-17F also promotes beiging and thermogenesis. The role of Treg cells in thermogenesis is controversial