Myeloid‐Derived Suppressor Cells in Adipose Tissue Homeostasis

Under steady‐state conditions, adipose tissue (AT) is highly metabolic, using free fatty acid (FFA) oxidation reactions to maintain an appropriate energy balance within the body. Even at relatively low concentrations, the by‐products of these reactions, such as reactive oxygen species (ROS), can lead to tissue damage and have been implicated as being partially responsible for inducing the chronic AT inflammation seen in obesity. This inflammation is also known to increase insulin resistance in the adipose, leading to diabetes. A network of adipose‐resident immune cells copes with this ever present threat of FFA oxidation and ROS induced inflammation with potent immunosuppressive mechanisms which help to maintain immune homeostasis within the tissue. During obesity, this homeostasis is disrupted by the infiltration of inflammatory cells into the adipose. This abject phenotypic switch of adipose‐resident immune cells has brought to light the importance of understanding how these cells work to maintain this initial homeostasis in lean adipose and what signals lead to the degradation of this immunosuppressive network during obesity. Initial flow cytometry data, from our lab's previous studies, revealed a functionally important population of CD11b+ Gr1+ stromal cells in the adipose. This surface marker combination, along with the anti‐inflammatory nature of lean adipose in general, led us to hypothesize that these cells were myeloid‐derived suppressor cells (MDSCs). MDSCs are a heterogeneous collection of immunosuppressive cells typically associated with cancer or chronic inflammatory diseases. We used flow cytometry to determine the surface marker expression profiles of the resident myeloid cells in the SVF, while CFSE and MTT assays were used to test the ability of SVF subsets to suppress proliferation of activated T cells. We found that approximately 2–3% of the adipose stroma expressed the classic CD11b hi Ly6C hi Ly6G − SSC low MDSC surface marker phenotype. Co‐culturing this population with activated T cells revealed their capacity to suppress T cell proliferation. Our findings suggest that there is a population of MDSCs resident in healthy adipose tissue. These potent immunosuppressive, endogenous adipose cells could represent a new therapeutic target for diabetes and obesity, as studies have already demonstrated that injections of culture‐derived MDSCs into obese mice increases insulin sensitivity and delays the development of metabolic syndromes. Support or Funding Information Kosair Charities