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. .

Department of Immunology Faculty of Medicine Tbilisi State Medical University Tbilisi Georgia

Department of Internal Medicine Dijon University Hospital Dijon France

Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences Prague Czechia

UBFC Inserm EFS BFC UMR1098 RIGHT Interactions Greffon Hôte Tumeur Ingénierie Cellulaire et Génique Besançon France

Université Bourgogne Franche Comté Inserm EFS BFC UMR1098 Team « immunoregulation immunopathology » RIGHT Interactions Greffon Hôte Tumeur Ingénierie Cellulaire et Génique Dijon France

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10.6084/m9.figshare.17128733.v1