Myeloid‐derived suppressor cells regulate T cell and B cell responses during autoimmune disease

M‐MDSCs inhibit autoreactive T and B cell function; reconstitution of CCR2‐deficient or wild‐type mice with M‐MDSCs ameliorates autoimmune arthritis. MDSCs are a heterogeneous group of myeloid cells that suppress T cell activity in cancer and autoimmune disease. The effect of MDSCs on B cell function is not clear. Using the CIA model of autoimmune disease, we found an increase in M‐MDSCs in the periphery of WT mice with CIA compared with nai¨ve mice. These MDSCs were absent from the periphery of CCR2−/− mice that developed exacerbated disease. M‐MDSCs, isolated from immunized mice, inhibited autologous CD4+ T cell proliferation. The M‐MDSC‐mediated suppression of T cell proliferation was NO and IFN‐γ dependent but IL‐17 independent. Furthermore, we demonstrated for the first time that M‐MDSCs from CIA mice also inhibited autologous B cell proliferation and antibody production. The suppression of B cells by M‐MDSCs was dependent on the production of NO and PGE2 and required cell–cell contact. Administration of M‐MDSCs rescued CCR2−/− mice from the exacerbated CIA phenotype and ameliorated disease in WT mice. Furthermore, adoptive transfer of M‐MDSCs reduced autoantibody production by CCR2−/− and WT mice. In summary, M‐MDSCs inhibit T cell and B cell function in CIA and may serve as a therapeutic approach in the treatment of autoimmune arthritis.