%0 Journal Article %T Mobilized Multipotent Hematopoietic Progenitors Promote Expansion and Survival of Allogeneic Tregs and Protect Against Graft Versus Host Disease %+ Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA) %+ Service d'Hématologie [CHRU Nancy] %+ Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)) %+ Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163) %+ Structure Fédérative de Recherche Necker (SFR Necker - UMS 3633 / US24) %+ Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy) %A d'Aveni, Maud %A Notarantonio, Anne-Béatrice %A Agbogan, Viviane, A %A Bertrand, Allan %A Fouquet, Guillemette %A Gastineau, Pauline %A Garfa-Traoré, Meriem %A de Carvalho, Marcelo %A Hermine, Olivier %A Rubio, Marie-Thérèse %A Zavala, Flora %< avec comité de lecture %@ 1664-3224 %J Frontiers in Immunology %I Frontiers %V 11 %N 607180 %8 2021-02-12 %D 2021 %R 10.3389/fimmu.2020.607180 %M 33643294 %K allogeneic HSCT %K graft versus host disease %K mobilization %K multipotent progenitors %K regulatory T cells %K expansion %K alloreactivity %K mixed lymphocyte reaction %Z Life Sciences [q-bio]/Immunology %Z Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]Journal articles %X Allogeneic Hematopoietic Stem Cell Transplantation (Allo-HSCT) is routinely performed with peripheral blood stem cells (PBSCs) mobilized by injection of G-CSF, a growth factor which not only modulates normal hematopoiesis but also induces diverse immature regulatory cells. Based on our previous evidence that G-CSF-mobilized multipotent hematopoietic progenitors (MPP) can increase survival and proliferation of natural regulatory T cells (Tregs) in autoimmune disorders, we addressed the question how these cells come into play in mice and humans in an alloimmune setting. Using a C57BL/6 mouse model, we demonstrate that mobilized MPP enhance the immunosuppressant effect exerted by Tregs, against alloreactive T lymphocytes, both in vitro and in vivo. They do so by migrating to sites of allopriming, interacting with donor Tregs and increasing their numbers, thus reducing the lethality of graft-versus-host disease (GVHD). Protection correlates likewise with increased allospecific Treg counts. Furthermore, we provide evidence for a phenotypically similar MPP population in humans, where it shares the capacity to promote selective Treg expansion in vitro. We postulate that G-CSF-mobilized MPPs might become a valuable cellular therapy to expand donor Tregs in vivo and prevent GVHD, thereby making allo-HSCT safer for the treatment of leukemia patients. %G English %2 https://u-paris.hal.science/hal-03253594/document %2 https://u-paris.hal.science/hal-03253594/file/MPP%20GVHD%20Frontiers.pdf %L hal-03253594 %U https://u-paris.hal.science/hal-03253594 %~ CNRS %~ APHP %~ UNIV-LORRAINE %~ IMOPA-UL %~ UNIV-PARIS %~ UNIVERSITE-PARIS %~ UP-SANTE %~ BMS-UL %~ IMOPA-EQ6