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. 2022 Mar 30;22(11):701–712. doi: 10.1038/s41577-022-00704-5

Fig. 3. ILC2s are involved in adipose tissue homeostasis.

Fig. 3

In mouse adipose tissue, sympathetic nerves and alternatively activated, M2-type macrophages produce noradrenaline that binds β-adrenergic receptors on mesenchymal adipose progenitor cells. This leads to their production of IL-33 and glial cell-derived neurotrophic factor (GDNF), for which the receptors ST2 and RET, respectively, are expressed on adipose tissue type 2 innate lymphoid cells (ILC2s). Activation of adipose tissue ILC2s leads to IL-4 and IL-13 production, which act on mesenchymal adipose cells to promote their production of the eosinophil chemotactic factor CCL11 (also known as eotaxin). Together with ILC2-derived IL-5, this recruits eosinophils to adipose tissue and supports their maintenance. Eosinophils produce IL-4 that supports the differentiation of alternatively activated macrophages, thereby creating a positive-feedback loop for a type 2 environment in the adipose tissue. Adipose tissue ILC2 activation also leads to the production of Met-Enkephalin (MetEnk), which acts on opioid receptors on adipocytes, resulting in a process known as beiging that reduces insulin resistance, a component of the metabolic syndrome.