Figure 2.

Th2 and Treg cell-mediated immune responses in VAT under the lean state. In the lean state, activation and proliferation of AT-resident Th2 and Treg cells are mediated by APCs including M2 macrophages, CD11c ^highF4/80⁻ ATDCs, and maybe adipocytes with low MHCII expression. Activated Th2 cells produce type 2 cytokines including IL-4, IL-5, and IL-13, which together with iNKT and Treg cell-produced IL-10 further stimulate M2 activation. IL-10 also acts directly on adipocytes to promote insulin sensitivity. The homeostasis of Th2 and Treg cells is promoted by constitutively produced IL-33 from Cdh11⁺ mesenchymal cells, Pdpn⁺ fibroblasts, and CD31⁺ endothelial cells via high expression of ST2 on the surface of both cells. In addition, IL-33 and IFN-γ counter-regulate ILC2 activation to control Treg cell numbers. Besides, iNKT cells are necessary to sustain Treg cells via the production of IL-2. Together, these pathways contribute to metabolically healthy VAT.