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Human fibrocytic myeloid‐derived suppressor cells express IDO and promote tolerance via Treg‐cell expansion
Authors:Alessia Zoso  Emilia M. C. Mazza  Silvio Bicciato  Susanna Mandruzzato  Vincenzo Bronte  Paolo Serafini  Luca Inverardi
Affiliation:1. Diabetes Research Institute, University of Miami, Miami, FL, USA;2. Department of Life Sciences, Center for Genome Research, University of Modena and Reggio Emilia, Modena, Italy;3. Department of Surgery, Oncology and Gastroenterology, Oncology and Immunology Section, University of Padova, Padova, Italy;4. Istituto Oncologico Veneto IOV – IRCCS, Padova, Italy;5. Department of Pathology, Immunology Section, Verona University Hospital, Verona, Italy;6. Department of Microbiology and Immunology, University of Miami, Miami, FL, USA
Abstract:By restraining T‐cell activation and promoting Treg‐cell expansion, myeloid‐derived suppressor cells (MDSCs) and tolerogenic DCs can control self‐reactive and antigraft effector T cells in autoimmunity and transplantation. Their therapeutic use and characterization, however, is limited by their scarce availability in the peripheral blood of tumor‐free donors. In the present study, we describe and characterize a novel population of human myeloid suppressor cells, named fibrocytic MDSC, which are differentiated from umbilical cord blood precursors by 4‐day culture with FDA‐approved cytokines (recombinant human‐GM‐CSF and recombinant human‐G‐CSF). This MDSC subset, characterized by the expression of MDSC‐, DC‐, and fibrocyte‐associated markers, promotes Treg‐cell expansion and induces normoglycemia in a xenogeneic mouse model of Type 1 diabetes. In order to exert their protolerogenic function, fibrocytic MDSCs require direct contact with activated T cells, which leads to the production and secretion of IDO. This new myeloid subset may have an important role in the in vitro and in vivo production of Treg cells for the treatment of autoimmune diseases, and in either the prevention or control of allograft rejection.
Keywords:Fibrocytes  Genomic analysis  IDO  Myeloid‐derived suppressor cells  Treg cells  Type 1 diabetes
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