Human Monocyte-Derived Suppressor Cell Supernatant Induces Immunoregulatory Effects and Mitigates xenoGvHD.

Fiche publication

Date publication

janvier 2022

Journal

Frontiers in immunology

Auteurs

Membres identifiés du Cancéropôle Est :
Pr ADOTEVI Olivier , Pr BONNOTTE Bernard

Tous les auteurs :
Gérard C, Thébault M, Lamarthée B, Genet C, Cattin F, Brazdova A, Janikashvili N, Cladière C, Ciudad M, Ouandji S, Ghesquière T, Greigert H, Tinel C, Adotevi O, Saas P, Samson M, Audia S, Bonnotte B

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/35345675

Résumé

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. , 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. .