Transfusion of CD206+ M2 Macrophages Ameliorates Antibody-Mediated Glomerulonephritis in Mice
Transfusion of CD206+ M2 Macrophages Ameliorates Antibody-Mediated Glomerulonephritis in Mice
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DOI：
10.1016/j.ajpath.2016.08.012
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发表时间：
2016-12-01
影响因子：
6
通讯作者：
Maruyama, Shoichi
中科院分区：
文献类型：
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作者：
Du, Qiuna;Tsuboi, Naotake;Maruyama, Shoichi
巨噬细胞是多功能的免疫细胞，可以驱动或调节疾病的发病机制，这取决于活化的表型。本研究探讨了CD 206（+）M2巨噬细胞对小鼠肾毒性血清肾炎的保护作用。我们发现，这些免疫抑制性巨噬细胞来源于骨髓，用IL-4/IL-13 [CD 206（+）M2骨髓源性巨噬细胞（M2 B1）]刺激，可保护肾损伤，减少蛋白尿，并减少CD 68（+）巨噬细胞、中性粒细胞和T细胞向肾小球组织的浸润。用来自诱导多能干细胞的CD 206（+）M2细胞获得了相当的治疗结果。值得注意的是，CD 206（+）M2 B细胞，它保留了M2的签名，可以引起M1到M2表型在共培养的巨噬细胞的开关。此外，发现这些细胞诱导脾和肾引流淋巴结中调节性T细胞的产生。因此，在来自用CD 206 + M2 B治疗的小鼠的肾脏中，T辅助细胞1细胞因子肿瘤坏死因子-α、干扰素-β、干扰素-γ和IL-12的mRNA表达显著降低。综上所述，这些数据表明，CD 206（+）M2可能对抗体介导的肾小球损伤具有治疗潜力，并对人类新月体肾炎的治疗具有治疗价值。
Macrophages are multifunctional immune cells that may either drive or modulate disease pathogenesis, depending on the activated phenotype. In this study, we investigated the protective effects of CD206(+) M2 macrophages against nephrotoxic serum nephritis in mice. We found that these immunosuppressive macrophages, derived from bone marrow and stimulated with IL-4/IL-13 [CD206(+) M2 bone marrow-derived macrophages (M2BMMs)], protected against renal injury, decreased proteinuria, and diminished the infiltration of CD68(+) macrophages, neutrophils, and T cells into glomerular tissue. Comparable therapeutic results were obtained with CD206(+) M2 cells derived from induced pluripotent stem cells. Notably, CD206(+) M2BMMs, which retained an M2 signature, could elicit a switch of M1 to M2 phenotype in co-cultured macrophages. Moreover, these cells were found to induce the production of regulatory T cells in the spleen and renal draining lymph node. Accordingly, mRNA expression of the T helper 1 cytokines tumor necrosis factor-alpha, interferon-beta, interferon-gamma, and IL-12 was significantly reduced in kidneys from mice treated with CD206+ M2BMMs. Taken together, the data suggest that CD206(+) M2 may have therapeutic potential against antibody-mediated glomerular injury and presents its therapeutic value for the treatment of crescentic nephritis in humans.