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Review
. 2018 Aug 10;19(8):2357.
doi: 10.3390/ijms19082357.

Myeloid-Derived Suppressor Cells as a Regulator of Immunity in Organ Transplantation

Tsukasa Nakamura  1 , Hidetaka Ushigome  2
Affiliations
Review

Myeloid-Derived Suppressor Cells as a Regulator of Immunity in Organ Transplantation

Tsukasa Nakamura et al. Int J Mol Sci. .

Abstract

Regulation of allo-immune responses is proposed as a topic for investigation in the current field of organ transplantation. As a regulator, regulatory T cells (Tregs) have received attention due to their ability to control allograft rejection. Concurrently, however, the independent action of Tregs is not enough to achieve tolerance status in many situations. Meanwhile, as a multi-functional regulator, myeloid-derived suppressor cells (MDSCs) can suppress effector T cells as well as induce Tregs or regulatory B cells (Bregs) in certain circumstances. Furthermore, the importance of a crosstalk between MDSCs and natural killer T cells to induce tolerance has been reported. Thus, orchestration between MDSCs, myeloid regulators, T/Bregs and other lymphoid/myeloid regulators can shed light on achieving allogeneic tolerance. Here, we review the current knowledge in terms of immunological regulatory function displayed by MDSCs in the context of organ transplantation. Ideal control of MDSCs would lead to a reduction of allograft rejection and subsequent long-term allograft acceptance.

Keywords: iNKT cells; myeloid-derived suppressor cells; organ transplantation; regulatory B cells; regulatory T cells; regulatory dendritic cells; regulatory macrophages; tolerance.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
MDSCs expansion is regulated by several factors in vivo microenvironment. This figure summarizes possible MDSCs inducers described in the context of transplantation and their signaling pathways. RAS is a target GTPase of CSF, TGF-β, or IL-6. mTOR inhibitor, rapamycin, paradoxically activates the RAS/RAF/MEK/ERK pathway. This pathway locates at a downstream of IL-33 and Steroid signaling pathways. Both cyclosporin and TCDD induce IDO through NFAT and aryl hydrocarbon receptor, respectively. The STAT 3 is mainly involved in MDSCs expansion as well as IDO expression. MDSCs, myeloid-derived suppressor cells; CSF, colony stimulating factor; IDO, indoleamine-2,3-dioxygenase; TCDD, 2,3,7,8-tetrachlorodibenzo-p-dioxin; NFAT, nuclear factor of activated T cells; STAT, signal transducer and activator of transcription.
Figure 2
Figure 2
MDSCs and their networks cooperatively protect allograft injury. Functional MDSCs produce a large amount of iNOS or arginase, resulting in effector T cell apoptosis, Tregs and Bregs and DCregs induction. MDSCs and invariant NKT cells interactions regulate the establishment of mixed chimerism. MDSCs, myeloid-derived suppressor cells; iNOS, inducible NO synthase; Tregs, regulatory T cells; Bregs, regulatory B cells; DCregs, regulatory dendritic cells; NKT, Natural Killer T cells.
See this image and copyright information in PMC

References

    1. Young M.R., Newby M., Wepsic H.T. Hematopoiesis and suppressor bone marrow cells in mice bearing large metastatic Lewis lung carcinoma tumors. Cancer Res. 1987;47:100–105. - PubMed
    1. Pak A.S., Wright M.A., Matthews J.P., Collins S.L., Petruzzelli G.J., Young M.R. Mechanisms of immune suppression in patients with head and neck cancer: Presence of CD34(+) cells which suppress immune functions within cancers that secrete granulocyte-macrophage colony-stimulating factor. Clin. Cancer Res. 1995;1:95–103. - PubMed
    1. Yang R., Cai Z., Zhang Y., Yutzy W.H., Roby K.F., Roden R.B. CD80 in immune suppression by mouse ovarian carcinoma-associated Gr-1+CD11b+ myeloid cells. Cancer Res. 2006;66:6807–6815. doi: 10.1158/0008-5472.CAN-05-3755. - DOI - PubMed
    1. Huang B., Pan P.Y., Li Q., Sato A.I., Levy D.E., Bromberg J., Divino C.M., Chen S.H. Gr-1+CD115+ immature myeloid suppressor cells mediate the development of tumor-induced T regulatory cells and T-cell anergy in tumor-bearing host. Cancer Res. 2006;66:1123–1131. doi: 10.1158/0008-5472.CAN-05-1299. - DOI - PubMed
    1. Dugast A.S., Haudebourg T., Coulon F., Heslan M., Haspot F., Poirier N., Vuillefroy de Silly R., Usal C., Smit H., Martinet B., et al. Myeloid-derived suppressor cells accumulate in kidney allograft tolerance and specifically suppress effector T cell expansion. J. Immunol. 2008;180:7898–7906. doi: 10.4049/jimmunol.180.12.7898. - DOI - PubMed