title: Identification of early myeloid progenitors as immunosuppressive cells.
abstract: Growing evidence suggests that hematopoietic stem/progenitor cells (HSPCs), precursors of mature immune cells, may play a direct role in immunosurveillance. Early myeloid progenitors are the major components of HSPCs and they often undergo extensive expansion in stress as a result of myeloid-biased hematopoiesis. Yet, the precise function of early myeloid progenitors remains unclear. Here we show that during tumor progression, mouse granulocyte/macrophage progenitors (GMPs) but not common myeloid progenitors (CMPs) are markedly expanded within the bone marrow and blood of mice. Interestingly, both GMPs and CMPs freshly isolated from either tumor-bearing or naïve animals are capable of inhibiting polyclonal stimuli- and alloantigen-induced T cell proliferation, with tumor host-derived cells having elevated activities. Strikingly, these early myeloid progenitor cells even display much stronger suppressive capacity than the classical myeloid-derived suppressive cells. Analysis of GMPs indicates that they express iNOS and can secrete high levels of NO. Further studies unusing iNOS specific inhibitors reveal that the immunosuppression of GMPs is, to a large extent, NO-dependent. GMPs can also efficiently induce regulatory T cell development. These studies demonstrate that early myeloid progenitors can act as immunosuppressive cells. This finding provides novel insights into the functional diversity and plasticity of early myeloid progenitor cells.
authors.affiliation: School of Life Sciences, Guangxi Normal University, Guilin 541004, China.|Guangxi Universities Key Laboratory of Stem cell and Biopharmaceutical Technology, Guangxi Normal University, Guilin 541004, China.
authors.forename: Shiming
authors.initials: S
authors.lastname: Pu
authors.affiliation: School of Life Sciences, Guangxi Normal University, Guilin 541004, China.
authors.forename: Baoxiong
authors.initials: B
authors.lastname: Qin
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Hospital/Institute, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing 100021, China.
authors.forename: Huan
authors.initials: H
authors.lastname: He
authors.affiliation: School of Life Sciences, Guangxi Normal University, Guilin 541004, China.
authors.forename: Jinxi
authors.initials: J
authors.lastname: Zhan
authors.affiliation: School of Life Sciences, Guangxi Normal University, Guilin 541004, China.|Guangxi Universities Key Laboratory of Stem cell and Biopharmaceutical Technology, Guangxi Normal University, Guilin 541004, China.|Research Center for Biomedical Sciences, Guangxi Normal University, Guilin 541004, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Wu
authors.affiliation: School of Life Sciences, Guangxi Normal University, Guilin 541004, China.|Research Center for Biomedical Sciences, Guangxi Normal University, Guilin 541004, China.
authors.forename: Xinming
authors.initials: X
authors.lastname: Zhang
authors.affiliation: School of Life Sciences, Guangxi Normal University, Guilin 541004, China.|Guangxi Universities Key Laboratory of Stem cell and Biopharmaceutical Technology, Guangxi Normal University, Guilin 541004, China.|Research Center for Biomedical Sciences, Guangxi Normal University, Guilin 541004, China.
authors.forename: Liu
authors.initials: L
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Hospital/Institute, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing 100021, China.
authors.forename: Chunfeng
authors.initials: C
authors.lastname: Qu
authors.affiliation: School of Life Sciences, Guangxi Normal University, Guilin 541004, China.|Guangxi Universities Key Laboratory of Stem cell and Biopharmaceutical Technology, Guangxi Normal University, Guilin 541004, China.|Research Center for Biomedical Sciences, Guangxi Normal University, Guilin 541004, China.
authors.forename: Zuping
authors.initials: Z
authors.lastname: Zhou
mesh_terms: D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D055014:Granulocyte-Macrophage Progenitor Cells / Q000276:immunology / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000276:immunology* / Q000378:metabolism; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D023461:Myeloid Progenitor Cells / Q000276:immunology* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism
chemical_list: D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II