Myeloid-derived suppressor cells regulate T cell and B cell responses during autoimmune disease #MMPMID25583578
Crook KR; Jin M; Weeks MF; Rampersad RR; Baldi RM; Glekas AS; Shen Y; Esserman DA; Little P; Schwartz TA; Liu P
J Leukoc Biol 2015[Mar]; 97 (3): 573-82 PMID25583578show ga
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 naive 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-gamma 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.
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J+Leukoc+Biol 2015 ; 97 (3): 573-82
