title: G-CSF mobilizes CD34+ regulatory monocytes that inhibit graft-versus-host disease.
abstract: Granulocyte colony-stimulating factor (G-CSF) is routinely used to collect peripheral blood stem cells (PBSCs) from healthy donors for allogeneic hematopoietic stem cell transplantation (allo-HSCT). We show that, in both humans and mice, G-CSF mobilizes a subset of CD34(+) cells with mature monocyte features. These cells, which are phenotypically and functionally conserved in mice and humans, are transcriptionally distinct from myeloid and monocytic precursors but similar to mature monocytes and endowed with immunosuppressive properties. In response to interferon-γ released by activated T cells, these cells produce nitric oxide, which induces allogeneic T cell death both in vitro and in vivo. These apoptotic T cells are engulfed by macrophages that release transforming growth factor-β and promote regulatory T cell expansion. Indeed, the fraction of CD34(+) monocytes in peripheral blood CD34(+) cells inversely correlates with the incidence of acute graft-versus-host disease (GVHD) in humans. Therefore, G-CSF-mobilized cells are an attractive candidate population to be expanded ex vivo for cellular therapy against GVHD.
authors.affiliation: INSERM U1163 and CNRS ERL 8254, Faculté de Médecine, Université Paris Descartes, Hôpital Necker, 75015 Paris, France. Faculté de Médecine and Université Paris-Sud, 94805 Villejuif, France. Institut Hospitalo-Universitaire Imagine, Université Sorbonne Paris Cité, Hôpital Necker, Assistance Publique-Hôpitaux de Paris, 75015 Paris, France.
authors.forename: Maud
authors.initials: M
authors.lastname: D'Aveni
authors.affiliation: INSERM U1163 and CNRS ERL 8254, Faculté de Médecine, Université Paris Descartes, Hôpital Necker, 75015 Paris, France. Faculté de Médecine and Université Paris-Sud, 94805 Villejuif, France. Institut Hospitalo-Universitaire Imagine, Université Sorbonne Paris Cité, Hôpital Necker, Assistance Publique-Hôpitaux de Paris, 75015 Paris, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Rossignol
authors.affiliation: INSERM U1163 and CNRS ERL 8254, Faculté de Médecine, Université Paris Descartes, Hôpital Necker, 75015 Paris, France. Faculté de Médecine and Université Paris-Sud, 94805 Villejuif, France. Institut Hospitalo-Universitaire Imagine, Université Sorbonne Paris Cité, Hôpital Necker, Assistance Publique-Hôpitaux de Paris, 75015 Paris, France.
authors.forename: Tereza
authors.initials: T
authors.lastname: Coman
authors.affiliation: Institute of Immunity and Transplantation, University College London, London NW3 2PF, UK. Cancer Institute, University College London, London WC1E 6DD, UK.
authors.forename: Shivajanani
authors.initials: S
authors.lastname: Sivakumaran
authors.affiliation: Cancer Institute, University College London, London WC1E 6DD, UK.
authors.forename: Stephen
authors.initials: S
authors.lastname: Henderson
authors.affiliation: Institute of Immunity and Transplantation, University College London, London NW3 2PF, UK. Cancer Institute, University College London, London WC1E 6DD, UK.
authors.forename: Teresa
authors.initials: T
authors.lastname: Manzo
authors.affiliation: Institute of Immunity and Transplantation, University College London, London NW3 2PF, UK. Cancer Institute, University College London, London WC1E 6DD, UK.
authors.forename: Pedro
authors.initials: P
authors.lastname: Santos e Sousa
authors.affiliation: INSERM U1163 and CNRS ERL 8254, Faculté de Médecine, Université Paris Descartes, Hôpital Necker, 75015 Paris, France. Institut Hospitalo-Universitaire Imagine, Université Sorbonne Paris Cité, Hôpital Necker, Assistance Publique-Hôpitaux de Paris, 75015 Paris, France. Laboratoire d'anatomopathologie, Groupe Hospitalier Necker-Enfants Malades, 75015 Paris, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Bruneau
authors.affiliation: INSERM U1163 and CNRS ERL 8254, Faculté de Médecine, Université Paris Descartes, Hôpital Necker, 75015 Paris, France. Faculté de Médecine and Université Paris-Sud, 94805 Villejuif, France. Institut Hospitalo-Universitaire Imagine, Université Sorbonne Paris Cité, Hôpital Necker, Assistance Publique-Hôpitaux de Paris, 75015 Paris, France.
authors.forename: Guillemette
authors.initials: G
authors.lastname: Fouquet
authors.affiliation: INSERM U1151, CNRS UMR8253, Institut Necker Enfants Malades, Université Paris Descartes, 75015 Paris, France.
authors.forename: Flora
authors.initials: F
authors.lastname: Zavala
authors.affiliation: INSERM U1163 and CNRS ERL 8254, Faculté de Médecine, Université Paris Descartes, Hôpital Necker, 75015 Paris, France.
authors.forename: Olinda
authors.initials: O
authors.lastname: Alegria-Prévot
authors.affiliation: Institut Fédératif de Recherche 94 Plateforme d'Imagerie Cellulaire, Faculté de Médecine, Université Paris Descartes, Hôpital Necker, 75015 Paris, France.
authors.forename: Meriem
authors.initials: M
authors.lastname: Garfa-Traoré
authors.affiliation: Service d'Hématologie Clinique, Hôpital Necker, Assistance Publique-Hôpitaux de Paris, 75015 Paris, France.
authors.forename: Felipe
authors.initials: F
authors.lastname: Suarez
authors.affiliation: Département de biothérapie, Groupe Hospitalier Pitié-Salpêtrière, 75013 Paris, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Trebeden-Nègre
authors.affiliation: Service d'Hématologie Clinique et de Thérapie Cellulaire, Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, 75012 Paris, France. INSERM UMRs 938, Centre de recherche de l'hôpital Saint Antoine, 75012 Paris, France. Université Pierre et Marie Curie, Paris VI, 75006 Paris, France.
authors.forename: Mohamad
authors.initials: M
authors.lastname: Mohty
authors.affiliation: Institute of Immunity and Transplantation, University College London, London NW3 2PF, UK. Cancer Institute, University College London, London WC1E 6DD, UK.
authors.forename: Clare L
authors.initials: CL
authors.lastname: Bennett
authors.affiliation: Institute of Immunity and Transplantation, University College London, London NW3 2PF, UK. Cancer Institute, University College London, London WC1E 6DD, UK.
authors.forename: Ronjon
authors.initials: R
authors.lastname: Chakraverty
authors.affiliation: INSERM U1163 and CNRS ERL 8254, Faculté de Médecine, Université Paris Descartes, Hôpital Necker, 75015 Paris, France. Institut Hospitalo-Universitaire Imagine, Université Sorbonne Paris Cité, Hôpital Necker, Assistance Publique-Hôpitaux de Paris, 75015 Paris, France. Service d'Hématologie Clinique, Hôpital Necker, Assistance Publique-Hôpitaux de Paris, 75015 Paris, France. mt_rubio@hotmail.com ohermine@gmail.com.
authors.forename: Olivier
authors.initials: O
authors.lastname: Hermine
authors.affiliation: INSERM U1163 and CNRS ERL 8254, Faculté de Médecine, Université Paris Descartes, Hôpital Necker, 75015 Paris, France. Institut Hospitalo-Universitaire Imagine, Université Sorbonne Paris Cité, Hôpital Necker, Assistance Publique-Hôpitaux de Paris, 75015 Paris, France. Service d'Hématologie Clinique et de Thérapie Cellulaire, Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, 75012 Paris, France. INSERM UMRs 938, Centre de recherche de l'hôpital Saint Antoine, 75012 Paris, France. Université Pierre et Marie Curie, Paris VI, 75006 Paris, France. mt_rubio@hotmail.com ohermine@gmail.com.
authors.forename: Marie-Thérèse
authors.initials: MT
authors.lastname: Rubio
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D006086:Graft vs Host Disease / Q000276:immunology*; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D019650:Hematopoietic Stem Cell Mobilization; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects; D007165:Immunosuppression Therapy; D007371:Interferon-gamma / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000187:drug effects; D014184:Transplantation, Homologous
chemical_list: D018952:Antigens, CD34; D016179:Granulocyte Colony-Stimulating Factor; D009569:Nitric Oxide; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II