Myeloid-derived suppressor cells regulate T cell and B cell responses during autoimmune disease
Myeloid-derived suppressor cells regulate T cell and B cell responses during autoimmune disease
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DOI：
10.1189/jlb.4a0314-139r
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发表时间：
2015-03-01
影响因子：
5.5
通讯作者：
Liu, Peng
中科院分区：
文献类型：
--
作者：
Crook, Kristen R.;Jin, Mengyao;Liu, Peng
MDSC是一组异质性骨髓细胞，可抑制癌症和自身免疫性疾病中的T细胞活性。MDSC对B细胞功能的影响尚不清楚。使用自身免疫性疾病的CIA模型，我们发现与幼稚小鼠相比，患有CIA的WT小鼠外周中的M-MDSC增加。这些MDSC不存在于发生恶化疾病的CCR 2（-/-）小鼠的外周。从免疫小鼠中分离的M-MDSC抑制自体CD 4（+）T细胞增殖。M-MDSC介导的T细胞增殖抑制是NO和IFN-γ依赖性的，但不依赖于IL-17。此外，我们首次证明了来自CIA小鼠的M-MDSC也抑制自体B细胞增殖和抗体产生。M-MDSC对B细胞的抑制依赖于NO和PGE的产生（2），并需要细胞-细胞接触。M-MDSC的施用拯救了CCR 2（-/-）小鼠免于恶化的CIA表型，并改善了WT小鼠的疾病。此外，M-MDSC的过继转移减少了CCR-/-和WT小鼠的自身抗体产生。总之，M-MDSC抑制CIA中的T细胞和B细胞功能，并可作为治疗自身免疫性关节炎的治疗方法。
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 PGE(2) 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 CCR-/- 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.