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

Abstract

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 vitro functional assays demonstrated that these cells suppressed αCD3/αCD28‐induced T‐cell proliferation, solidifying their identity as bona fide adipose‐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 of bona fide MDSCs in the adipose of otherwise healthy mice that actively contribute to the health and immune homeostasis of this tissue.