Adipose-resident myeloid-derived suppressor cells modulate immune cell homeostasis in healthy mice.

The metabolically dynamic nature of healthy adipose places this tissue under regular inflammatory stress. A network of adipose-resident anti-inflammatory immune cells modulates and resolves this endogenous inflammation. Previous work in our laboratory identified a CD11b(+)Gr1(+)subset of these immunosuppressive adipose stromal cells in healthy mice. Myeloid-derived suppressor cells (MDSCs), typically associated with cancer and chronic inflammation, have a similar surface marker phenotype and accumulate in adipose of high-fat diet-fed mice. Given the routine inflammatory stresses on healthy adipose and the suppressive nature of the tissue-resident immune cells, we hypothesized that these CD11b(+)Gr1(+)cells were a genuine population of MDSCs involved in regulating tissue homeostasis. Flow cytometric analysis of these cells found that they were CD11b(+)CD301(-)Ly6C(+)Ly6G(+/-)and did not express traditional macrophage markers. Moreover,in vitrofunctional assays demonstrated that these cells suppressed alpha CD3/alpha CD28-induced T-cell proliferation, solidifying their identity asbona fideadipose-resident MDSCs. Systemic MDSC depletion altered adipose immune cell dynamics in otherwise healthy mice, increasing the number of CD4(+)effector memory T cells and modifying the surface markers expressed by adipose-resident macrophages. In addition, transcription of various immunomodulatory cytokines was clearly dysregulated in the adipose of MDSC-depleted animals compared with controls. Altogether, our findings indicate that there is a population ofbona fideMDSCs in the adipose of otherwise healthy mice that actively contribute to the health and immune homeostasis of this tissue.