In:
Journal of Leukocyte Biology, Oxford University Press (OUP), Vol. 97, No. 3 ( 2015-03-01), p. 573-582
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 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.
Type of Medium:
Online Resource
ISSN:
0741-5400
,
1938-3673
DOI:
10.1189/jlb.4A0314-139R
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
2015
detail.hit.zdb_id:
2026833-6
SSG:
12
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