CD24 is expressed on FoxP3⁺ regulatory T cells and regulates their function

CD24 is a glycosyl-phosphatidylinositol (GPI) anchored cell surface glycoprotein with a variety of immunomodulatory functions such as inhibition of thymic generation of autoreactive T cells, regulation of antigen presenting cell functions, and mediation of autoimmunity. Given the autoimmune nature of FoxP3⁺ regulatory T cells and their importance in autoimmune diseases, we hypothesize that CD24 regulates the generation and functions of Treg cells. Through the analysis of the Treg repertoire in two strains of CD24-deficient mice, we found that CD24 does not globally affect the thymic generation of Treg cells. However, CD24 is abundantly expressed on Treg cells, and CD24 antibody treatment of Treg cells enhances their suppressive functions. Concurrently, we observed CD24-deficient Treg cells exhibit increased suppressive functions and produce more IL-10 compared to their wild type counterparts. In addition, CD24-deficient Treg cells exhibited more potent suppressive capacity in inhibiting the development of experimental autoimmune encephalomyelitis (EAE) in mice. Thus, CD24 on Treg cells regulates their suppressive functions. Our findings can partially explain the resistance of EAE development in CD24-deficient mice and CD24 polymorphism-associated susceptibility of human autoimmune diseases. Further investigations regarding mechanisms of CD24 regulation of Treg function may lead to a new approach for the immunotherapy of human autoimmune diseases.