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Biochem Biophys Res Commun. 2017 Dec 9;494(1-2):6-12. doi: 10.1016/j.bbrc.2017.10.097. Epub 2017 Oct 19.

Ly6Chi monocytes are required for mesenchymal stem/stromal cell-induced immune tolerance in mice with experimental autoimmune uveitis.

Author information

1
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.
2
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. Electronic address: jooyounoh77@gmail.com.

Abstract

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 IIhiB220hiCD11bmid 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 CD11bhiLy6Chi monocytes are precursors to MHC IIhiB220hiCD11bmid 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 IIhiB220hiCD11bmid macrophages in the lung with a concomitant decrease in CD11bhiLy6Chi monocytes. Selective depletion of circulating CD11bhiLy6Chi cells abrogated the effects of MSC in the induction of IL-10hiMHC IIhiB220hiCD11bmid macrophages and immune tolerance in EAU mice. Similarly, an increase in CD4+CD25+Foxp3+ Tregs by MSCs was also reversed by CD11bhiLy6Chi cell depletion. These results suggest that CD11bhiLy6Chi monocytes are critical for MSC-induced immune tolerance.

KEYWORDS:

Experimental autoimmune uveitis; Immune tolerance; Ly6C(hi) monocyte; Mesenchymal stem/stromal cell; Regulatory T cell; Suppressive macrophage

PMID:
29056505
DOI:
10.1016/j.bbrc.2017.10.097
[Indexed for MEDLINE]

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