AUTHOR=Gérard Claire , Thébault Marine , Lamarthée Baptiste , Genet Coraline , Cattin Florine , Brazdova Andréa , Janikashvili Nona , Cladière Claudie , Ciudad Marion , Ouandji Séthi , Ghesquière Thibault , Greigert Hélène , Tinel Claire , Adotevi Olivier , Saas Philippe , Samson Maxime , Audia Sylvain , Bonnotte Bernard TITLE=Human Monocyte-Derived Suppressor Cell Supernatant Induces Immunoregulatory Effects and Mitigates xenoGvHD JOURNAL=Frontiers in Immunology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.827712 DOI=10.3389/fimmu.2022.827712 ISSN=1664-3224 ABSTRACT=

Recently developed cell-based therapies have shown potential for graft-versus-host disease (GvHD) mitigation. Our team previously developed a protocol to generate human monocyte-derived suppressor Cells (HuMoSC), a subpopulation of CD33+ suppressor cells of monocytic origin. CD33+HuMoSC successfully reduced xenoGvHD severity in NOD/SCID/IL-2Rγc-/- (NSG) mice. While CD33+ HuMoSC culture supernatant inhibits T cell activation and proliferation, the recovery of CD33+ HuMoSC immunosuppressive cells and the subsequent production of their supernatant is limited. An attractive solution would be to use both the CD33+ and the large number of CD14+ cells derived from our protocol. Here, we assessed the immunoregulatory properties of the CD14+HuMoSC supernatant and demonstrated that it inhibited both CD4 and CD8 T cell proliferation and decreased CD8 cytotoxicity. In vivo, injection of CD14+HuMoSC supernatant reduced xenoGvHD in NSG mice. Furthermore, CD14+HuMoSC supernatant maintained its immunoregulatory properties in an inflammatory environment. Proteomic and multiplex analyses revealed the presence of immunosuppressive proteins such as GPNMB, galectin-3 and IL-1R(A) Finally, CD14+HuMoSC supernatant can be produced using good manufacturing practices and be used as complement to current immunosuppressive drugs. CD14+HuMoSC supernatant is thus a promising therapy for preventing GvHD.