Ko Jung Hwa, Lee Hyun Ju, Jeong Hyun Jeong, Oh Joo Youn
Department of Ophthalmology, Seoul National University Hospital, 101, Daehak-ro, Jongno-gu, Seoul, 03080, South Korea; Laboratory of Ocular Regenerative Medicine and Immunology, Biomedical Research Institute, Seoul National University Hospital, 101, Daehak-ro, Jongno-gu, Seoul, 03080, South Korea.
Department of Ophthalmology, Seoul National University Hospital, 101, Daehak-ro, Jongno-gu, Seoul, 03080, South Korea; Laboratory of Ocular Regenerative Medicine and Immunology, Biomedical Research Institute, Seoul National University Hospital, 101, Daehak-ro, Jongno-gu, Seoul, 03080, South Korea.
Biochem Biophys Res Commun. 2017 Dec 9;494(1-2):6-12. doi: 10.1016/j.bbrc.2017.10.097. Epub 2017 Oct 19.
The cells of the innate immune system, in addition to their capacity to elicit immunity, play a substantial role in immune tolerance induction. Our group has recently shown that a distinct subset of MHC IIB220CD11b suppressive macrophages is increased in the lung by intravenous (IV) administration of mesenchymal stem/stromal cells (MSC) and induces immune tolerance. Herein, we demonstrate that circulating CD11bLy6C monocytes are precursors to MHC IIB220CD11b macrophages in the lung and required for MSC-induced tolerance in a mouse model of experimental autoimmune uveitis (EAU). Analysis revealed that IV MSC induced an increase in IL-10-expressing MHC IIB220CD11b macrophages in the lung with a concomitant decrease in CD11bLy6C monocytes. Selective depletion of circulating CD11bLy6C cells abrogated the effects of MSC in the induction of IL-10MHC IIB220CD11b macrophages and immune tolerance in EAU mice. Similarly, an increase in CD4CD25Foxp3 Tregs by MSCs was also reversed by CD11bLy6C cell depletion. These results suggest that CD11bLy6C monocytes are critical for MSC-induced immune tolerance.
固有免疫系统的细胞，除了具有引发免疫的能力外，在免疫耐受诱导中也发挥着重要作用。我们的研究小组最近发现，通过静脉注射间充质干细胞（MSC），肺中一种独特的MHC IIB220CD11b抑制性巨噬细胞亚群会增加，并诱导免疫耐受。在此，我们证明循环中的CD11bLy6C单核细胞是肺中MHC IIB220CD11b巨噬细胞的前体，并且在实验性自身免疫性葡萄膜炎（EAU）小鼠模型中是MSC诱导耐受所必需的。分析显示，静脉注射MSC会导致肺中表达IL-10的MHC IIB220CD11b巨噬细胞增加，同时CD11bLy6C单核细胞减少。选择性清除循环中的CD11bLy6C细胞消除了MSC在EAU小鼠中诱导IL-10MHC IIB220CD11b巨噬细胞和免疫耐受的作用。同样，CD11bLy6C细胞的清除也逆转了MSC导致的CD4CD25Foxp3调节性T细胞增加。这些结果表明，CD11bLy6C单核细胞对MSC诱导的免疫耐受至关重要。
