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Myeloid‐derived suppressor cells improve corneal graft survival through suppressing angiogenesis and lymphangiogenesis
Author(s) -
Ren Yuerong,
Dong Xiaonan,
Zhao Han,
Feng Jianing,
Chen Baihua,
Zhou Yedi,
Peng Yingqian,
Zhang Liwei,
Zhou Qinghua,
Li Yunping,
Wu Mengbo,
He Yan
Publication year - 2021
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.16291
Subject(s) - medicine , lymphangiogenesis , angiogenesis , neovascularization , cancer research , myeloid derived suppressor cell , transplantation , immunology , vascular endothelial growth factor , foxp3 , immune system , cancer , suppressor , metastasis , vegf receptors
Myeloid‐derived suppressor cells (MDSC) are one of the major negative regulators of immune responses during many pathological conditions such as cancer and transplantation. Emerging evidence indicates that MDSC also contribute to tumor progression through their pro‐angiogenic activity in addition to immunosuppressive function. However, virtually nothing is known about the role of MDSC in the regulation of neovascularization after transplantation. Here we showed that antibody‐mediated depletion of MDSC in mice led to robust growth of blood and lymphatic neovessels and rapid allograft rejection after corneal penetrating keratoplasty. In contrast, adoptive transfer of ex vivo generated MDSC from cytokine‐treated bone marrow cells (evMDSC) suppressed neovascularization and prolonged corneal allograft survival in an inducible nitric oxide synthase (iNOS)‐dependent manner. Mechanistically, compared to naïve MDSC control, evMDSC have increased expression of an anti‐angiogenic factor thrombospondin 1 (Tsp‐1) and decreased expression of two critical pro‐angiogenic factors, vascular endothelial growth factor A (VEGF‐A), and VEGF‐C. These findings demonstrate MDSC as a critical anti‐angiogenic regulator during transplantation. Our study also indicates that evMDSC are a valuable candidate agent for development of novel cell therapy to improve allograft survival after transplantation.