Fig. 3 |. Cellular crosstalk between immune cells and other adipose-resident cells.

Adipose tissue-resident immune cells are major contributors to the adipose niche by playing key roles in both the function of brown adipose tissue (BAT) and white adipose tissue (WAT) and homeostasis through extensive cellular crosstalk with other cell types. M1 macrophages (dark blue) secrete pro-inflammatory cytokines (pale red) that impair insulin signalling and suppress thermogenesis in adipocytes. Conversely, a type 2 immune response, which is mediated by M2 macrophages (yellow), eosinophils (red), innate lymphoid type 2 cells (ILC2, grey) and invariant natural killer T-cells (iNKTs, green), enhances BAT activation and browning of WAT (factors involved in the type 2 responses are shown in pale blue). Thermogenic adipocytes (shown in beige and brown) regulate the type 2 immune response by releasing ADIPOQ, CXCL14, GDF15, METRNL and CCL11 (adipocyte-released factors are shown in pale yellow). A multicellular communication axis between sympathetic nerves, adipocytes, eosinophils, adipocyte progenitors and macrophages also orchestrates the adaptive response of WAT to cold. Methionine-enkephalin (MET-ENK) are IL2C-derived secreted peptides that induce uncoupling protein 1 expression in white adipocytes. Sympathetic neuron-associated macrophages (SAMs) mediate the clearance of extracellular noradrenaline (NE, grey) and thereby negatively regulate NE availability and the thermogenic activity of BAT and beige adipose tissue. ADIPOQ, adiponectin; CCL11, chemokine (C-C motif) ligand 11; CXCL14, C-X-C motif chemokine ligand 14; FGF, fibroblast growth factor; GDF15, growth differentiation factor 15; METRNL, meteorin-like glial cell differentiation regulator; PDGF, platelet-derived growth factor; TNF, tumour necrosis factor.