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

Autor: Crook KR; Thurston Arthritis Research Center and Departments of Biostatistics and Medicine, University of North Carolina at Chapel Hill, North Carolina, USA., Jin M; Thurston Arthritis Research Center and Departments of Biostatistics and Medicine, University of North Carolina at Chapel Hill, North Carolina, USA., Weeks MF; Thurston Arthritis Research Center and Departments of Biostatistics and Medicine, University of North Carolina at Chapel Hill, North Carolina, USA., Rampersad RR; Thurston Arthritis Research Center and Departments of Biostatistics and Medicine, University of North Carolina at Chapel Hill, North Carolina, USA., Baldi RM; Thurston Arthritis Research Center and Departments of Biostatistics and Medicine, University of North Carolina at Chapel Hill, North Carolina, USA., Glekas AS; Thurston Arthritis Research Center and Departments of Biostatistics and Medicine, University of North Carolina at Chapel Hill, North Carolina, USA., Shen Y; Thurston Arthritis Research Center and Departments of Biostatistics and Medicine, University of North Carolina at Chapel Hill, North Carolina, USA., Esserman DA; Thurston Arthritis Research Center and Departments of Biostatistics and Medicine, University of North Carolina at Chapel Hill, North Carolina, USA., Little P; Thurston Arthritis Research Center and Departments of Biostatistics and Medicine, University of North Carolina at Chapel Hill, North Carolina, USA., Schwartz TA; Thurston Arthritis Research Center and Departments of Biostatistics and Medicine, University of North Carolina at Chapel Hill, North Carolina, USA., Liu P; Thurston Arthritis Research Center and Departments of Biostatistics and Medicine, University of North Carolina at Chapel Hill, North Carolina, USA liupz@med.unc.edu.
Jazyk: angličtina
Zdroj: Journal of leukocyte biology [J Leukoc Biol] 2015 Mar; Vol. 97 (3), pp. 573-82. Date of Electronic Publication: 2015 Jan 12.
DOI: 10.1189/jlb.4A0314-139R
Abstrakt: 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.
(© Society for Leukocyte Biology.)
Databáze: MEDLINE
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