Department of Ophthalmology, Seoul National University Hospital, Seoul 03080, Korea.
Laboratory of Ocular Regenerative Medicine and Immunology, Seoul Artificial Eye Center, Seoul National University Hospital Biomedical Research Institute, Seoul 03080, Korea.
J Immunol. 2018 Feb 15;200(4):1306-1315. doi: 10.4049/jimmunol.1700617. Epub 2018 Jan 8.
Resolution of inflammation is an active process that leads to tissue homeostasis and involves multiple cellular and molecular mechanisms. Myeloid-derived suppressor cells (MDSCs) have recently emerged as important cellular components in the resolution of inflammation because of their activities to suppress T cell activation. In this article, we show that HLA-DRCD11bCD33CD14 human MDSCs and CD11bLy6GLy6C mouse MDSCs markedly increased in patients and mice during and before the resolution phase of autoimmune uveoretinitis. CD11bLy6C monocytes isolated from autoimmune uveoretinitis mice were able to suppress T cell proliferation in culture, and adoptive transfer of the cells accelerated the remission of autoimmune uveoretinitis in mice. Alternatively, depletion of CD11bLy6C monocytes at the resolution phase, but not CD11bLy6G granulocytes, exacerbated the disease. These findings collectively indicate that monocytic MDSCs serve as regulatory cells mediating the resolution of autoimmune uveoretinitis.
炎症消退是一个主动的过程,它导致组织的内稳态,并涉及多种细胞和分子机制。髓源性抑制细胞(MDSCs)因其抑制 T 细胞激活的作用而成为炎症消退过程中的重要细胞成分。在本文中,我们发现在自身免疫性葡萄膜炎的消退阶段及其前后,患者和小鼠的 HLA-DRCD11bCD33CD14 人 MDSCs 和 CD11bLy6GLy6C 小鼠 MDSCs 明显增加。从自身免疫性葡萄膜炎小鼠中分离出的 CD11bLy6C 单核细胞能够在培养中抑制 T 细胞增殖,并且细胞的过继转移加速了小鼠自身免疫性葡萄膜炎的缓解。相反,在消退阶段耗尽 CD11bLy6C 单核细胞(而非 CD11bLy6G 粒细胞)会使疾病恶化。这些发现共同表明,单核 MDSCs 作为调节细胞,介导自身免疫性葡萄膜炎的消退。