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.

Keywords: Adipose tissue-resident macrophages; CD4+ effector memory T cells; MDSCs; tissue homeostasis.