Immune regulation by apoptotic cell clearance
Immune regulation by apoptotic cell clearance
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DOI：
10.1111/j.1749-6632.2010.05746.x
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发表时间：
2010-10
影响因子：
5.2
通讯作者：
Masato Tanaka;K. Asano;Chunhong Qiu
中科院分区：
文献类型：
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作者：
Masato Tanaka;K. Asano;Chunhong Qiu
吞噬细胞的凋亡清除对于维持生理条件下的自我耐受是必不可少的。与此一致的是，静脉注射凋亡细胞可以诱导细胞相关抗原特异性免疫抑制或耐受。静脉注射凋亡细胞表达髓鞘少突胶质细胞糖蛋白(MOG)诱导的MOG特异性T细胞耐受片段，抑制实验性自身免疫性脑脊髓炎的发生发展。然而，暴露在凋亡细胞上的磷脂酰丝氨酸(PS)可基本消除表达MOG的凋亡细胞的抑制作用，这表明PS依赖的凋亡细胞吞噬是耐受诱导所必需的。我们发现，这种耐受诱导机制需要脾边缘带(MZ)的两个细胞群的贡献。MZ含有两种类型的巨噬细胞：边缘嗜金属巨噬细胞和MZ巨噬细胞。这些巨噬细胞有助于快速清除血流中的细胞身体。此外，我们还发现定位于MZ的CD8α+、CD103+树突状细胞选择性地吞噬血源性死亡细胞，并随后呈递死亡细胞相关抗原，从而诱导抗原特异性免疫抑制或耐受。
Apoptotic cell clearance by phagocytes is essential for the maintenance of self‐tolerance under physiological conditions. Consistent with this, the intravenous injection of apoptotic cells can induce cell‐associated antigen‐specific immunosuppression or tolerance. The intravenous injection of apoptotic cells expressed a fragment of myelin oligodendrocyte glycoprotein (MOG)‐induced MOG‐specific T cell tolerance and suppressed the development of experimental autoimmune encephalomyelitis. However, the suppressive effects of the MOG‐expressing apoptotic cells were largely eliminated by masking phosphatidylserine (PS) exposed on the apoptotic cells, suggesting that the PS‐dependent engulfment of apoptotic cells is required for the tolerance induction. We found that this mechanism of tolerance induction requires the contribution of two cell populations in the splenic marginal zone (MZ). The MZ contains two types of macrophages: marginal metallophilic macrophages and MZ macrophages. These macrophages contribute to the rapid clearance of cell corpses in blood flow. In addition, we also found that CD8α+, CD103+ dendritic cells localizing in the MZ selectively phagocytose blood‐borne dead cells and subsequently present dead cell‐associated antigens to induce antigen‐specific immunosuppression or tolerance.