Involvement of CD11b+ GR-1low cells in autoimmune disorder in MRL-Fas lpr mouse
Involvement of CD11b+ GR-1low cells in autoimmune disorder in MRL-Fas lpr mouse
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DOI：
10.1007/s10157-010-0309-9
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发表时间：
2010-10-01
影响因子：
2.3
通讯作者：
Wada, Takashi
中科院分区：
文献类型：
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作者：
Iwata, Yasunori;Furuichi, Kengo;Wada, Takashi
骨髓源性抑制细胞（MDSC）已被确定为肿瘤相关炎症中的免疫抑制细胞。然而，MDSCs 导致自身免疫性疾病的发病机制尚未得到研究。本研究的目的是探讨 MDSC 是否会导致狼疮易发小鼠的自身免疫器官损伤。通过 MRL-Fas (lpr) 小鼠中 CD11b(+) GR-1(+) 的流式细胞术染色来分析 MDSC。通过与CD11b(+)GR-1(+)脾细胞共培养进行CD4(+)T细胞增殖测定。在疾病进展过程中检查免疫抑制细胞的百分比。分析免疫抑制细胞上趋化因子受体的表达，并进行趋化实验。CD11b(+)GR-1(low)细胞对CD4(+)T细胞增殖有抑制作用，精氨酸酶1抑制剂可恢复这种作用。 CD11b(+) GR-1(低) 细胞在肾脏和血液疾病进展期间百分比增加。在单核细胞趋化蛋白-1/CCL2存在下，迁移的CD11b(+) GR-1(低)细胞的数量增加。我们评估了CD11b(+) GR-1(低)细胞在MRL-Fas (lpr)小鼠自身免疫性疾病中的参与情况。这些细胞通过 CCL2/CCR2 信号传导调节免疫反应。免疫抑制单核细胞的调节可能为自身免疫性疾病器官损伤提供新的治疗策略。
Myeloid-derived suppressor cells (MDSCs) have been identified as immunosuppressive cells in tumor-related inflammation. However, the pathogenesis of MDSCs for autoimmune disease has not been investigated as yet. The aim of this study was to address whether MDSCs contribute to autoimmune organ injury in lupus-prone mice.MDSCs were analyzed by flow cytometric staining of CD11b(+) GR-1(+) in MRL-Fas (lpr) mice. CD4(+) T-cell proliferation assay was performed by coculture with CD11b(+) GR-1(+) splenocytes. The percentage of immunosuppressive cells was examined during disease progression. Expression of chemokine receptor on immunosuppressive cells was analyzed, and chemotaxis assay was performed.CD11b(+) GR-1(low) cells had a suppressive effect on CD4(+) T-cell proliferation, which was restored by an arginase-1 inhibitor. CD11b(+) GR-1(low) cells increased in percentage during disease progression in kidney and blood. The number of migrated CD11b(+) GR-1(low) cells increased in the presence of monocyte chemoattractant protein-1/CCL2.We assessed the involvement of CD11b(+) GR-1(low) cells in autoimmune disorder in MRL-Fas (lpr) mice. These cells regulate immunological responses via CCL2/CCR2 signaling. The regulation of immunosuppressive monocytes may provide novel therapeutic strategy for organ damage in autoimmune diseases.