title: Myeloid-derived suppressor cells regulate T cell and B cell responses during autoimmune disease.
abstract: 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 naïve 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.
authors.affiliation: *Thurston Arthritis Research Center and Departments of Biostatistics and Medicine, University of North Carolina at Chapel Hill, North Carolina, USA.
authors.forename: Kristen R
authors.initials: KR
authors.lastname: Crook
authors.affiliation: *Thurston Arthritis Research Center and Departments of Biostatistics and Medicine, University of North Carolina at Chapel Hill, North Carolina, USA.
authors.forename: Mengyao
authors.initials: M
authors.lastname: Jin
authors.affiliation: *Thurston Arthritis Research Center and Departments of Biostatistics and Medicine, University of North Carolina at Chapel Hill, North Carolina, USA.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Weeks
authors.affiliation: *Thurston Arthritis Research Center and Departments of Biostatistics and Medicine, University of North Carolina at Chapel Hill, North Carolina, USA.
authors.forename: Rishi R
authors.initials: RR
authors.lastname: Rampersad
authors.affiliation: *Thurston Arthritis Research Center and Departments of Biostatistics and Medicine, University of North Carolina at Chapel Hill, North Carolina, USA.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Baldi
authors.affiliation: *Thurston Arthritis Research Center and Departments of Biostatistics and Medicine, University of North Carolina at Chapel Hill, North Carolina, USA.
authors.forename: Amy S
authors.initials: AS
authors.lastname: Glekas
authors.affiliation: *Thurston Arthritis Research Center and Departments of Biostatistics and Medicine, University of North Carolina at Chapel Hill, North Carolina, USA.
authors.forename: Yajuan
authors.initials: Y
authors.lastname: Shen
authors.affiliation: *Thurston Arthritis Research Center and Departments of Biostatistics and Medicine, University of North Carolina at Chapel Hill, North Carolina, USA.
authors.forename: Denise A
authors.initials: DA
authors.lastname: Esserman
authors.affiliation: *Thurston Arthritis Research Center and Departments of Biostatistics and Medicine, University of North Carolina at Chapel Hill, North Carolina, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Little
authors.affiliation: *Thurston Arthritis Research Center and Departments of Biostatistics and Medicine, University of North Carolina at Chapel Hill, North Carolina, USA.
authors.forename: Todd A
authors.initials: TA
authors.lastname: Schwartz
authors.affiliation: *Thurston Arthritis Research Center and Departments of Biostatistics and Medicine, University of North Carolina at Chapel Hill, North Carolina, USA liupz@med.unc.edu.
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D001169:Arthritis, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D015232:Dinoprostone / Q000378:metabolism; D005260:Female; D007114:Immunization; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009000:Monocytes / Q000473:pathology; D022423:Myeloid Cells / Q000276:immunology* / Q000637:transplantation; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010641:Phenotype; D054390:Receptors, CCR2 / Q000172:deficiency / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: C515335:Ccr2 protein, mouse; D020381:Interleukin-17; D054390:Receptors, CCR2; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II; D015232:Dinoprostone
keywords: autoimmune arthritis; chemokine receptor; collagen-induced arthritis; immunotherapy; rheumatoid arthritis