Impact of myeloid-derived suppressor cells on adoptive immunity in autoimmune arthritis (THER5P.827)

Abstract

Abnormal B- and T-cell recognition of self-antigens and autoantibody production result in autoimmunity. We previously showed that myeloid-derived suppressor cells (MDSCs) suppress T cell proliferation in autoimmune arthritis. To further explore the impact of MDSCs on B cells, we examined B cell functions in vitro and in vivo in collagen-induced arthritis. We found the proliferation of collagen-primed B cells was inhibited by autologous monocytic MDSCs, but not by Ly6G+ neutrophils. The production of both IgG and IgM was reduced in the supernatant of B cell and monocytic MDSC co-cultures as compared to the supernatant from B cells alone or the supernatant from B cell-Ly6G+ cell co-cultures. Mechanistically, the levels of iNOS and PGE2 increased in the B cell-MDSC co-cultures, and addition of either iNOS or PGE2 inhibitors abolished the MDSC suppression of B cell proliferation. While neutralizing IL-12 also reestablished B cell proliferation, blockade of IL-6 and TNFa did not show similar effect. Finally, adoptive transfer of monocytic MDSCs to collagen-immunized mice resulted in reduced autoantibody production and mitigated arthritis severity. In summary our data show that monocytic MDSCs suppress autoreactive B cell proliferation and antibody production. The suppressive function requires iNOS, PGE2 and IL-12, but is independent of IL-6 and TNFa. These MDSCs can potentially be used in cell-based therapy to treat autoimmune arthritis by limiting B cell functions.