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CD11b + Ly6G + myeloid‐derived suppressor cells promote liver regeneration in a murine model of major hepatectomy
Author(s) -
Nachmany Ido,
Bogoch Yoel,
Sivan Ayelet,
Amar Omer,
Bondar Ekaterina,
Zohar Nitzan,
Yakubovsky Oran,
Fainaru Ofer,
Klausner Joseph M.,
Pencovich Niv
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201801733r
Subject(s) - liver regeneration , angiogenesis , myeloid derived suppressor cell , neovascularization , cancer research , regeneration (biology) , biology , hepatocyte , hepatectomy , immunology , microbiology and biotechnology , suppressor , medicine , cancer , biochemistry , genetics , in vitro , surgery , resection
Liver regeneration depends on sequential activation of pathways and cells involving the remaining organ in recovery of mass. Proliferation of parenchyma is dependent on angiogenesis. Understanding liver regeneration–associated neovascularization may be useful for development of clinical interventions. Myeloid‐derived suppressor cells (MDSCs) promote tumor angiogenesis and play a role in developmental processes that necessitate rapid vascularization. We therefore hypothesized that the MDSCs could play a role in liver regeneration. Following partial hepatectomy, MDSCs were enriched within regenerating livers, and their depletion led to increased liver injury and postoperative mortality, reduced liver weights, decreased hepatic vascularization, reduced hepatocyte hypertrophy and proliferation, and aberrant liver function. Gene expression profiling of regenerating liver‐derived MDSCs demonstrated a large‐scale transcriptional response involving key pathways related to angiogenesis. Functionally, enhanced reactive oxygen species production and angiogenic capacities of regenerating liver‐derived MDSCs were confirmed. A comparative analysis revealed that the transcriptional response of MDSCs during liver regeneration resembled that of peripheral blood MDSCs during progression of abdominal tumors, suggesting a common MDSC gene expression profile promoting angiogenesis. In summary, our study shows that MDSCs contribute to early stages of liver regeneration possibly by exerting proangiogenic functions using a unique transcriptional program.—Nachmany, I., Bogoch, Y., Sivan, A., Amar, O., Bondar, E., Zohar, N., Yakubovsky, O., Fainaru, O., Klausner, J. M., Pencovich, N. CD11b + Ly6G + myeloid‐derived suppressor cells promote liver regeneration in a murine model of major hepatectomy. FASEB J. 33, 5967–5978 (2019). www.fasebj.org