Interleukin-27 Promotes the Generation of Myeloid-derived Suppressor Cells to Alleviate Graft-versus-host Disease.
Transplantation
; 2024 May 21.
Article
en En
| MEDLINE
| ID: mdl-38773837
ABSTRACT
BACKGROUND:
Stimulation of myeloid-derived suppressor cell (MDSC) formation represents a potential curative therapeutic approach for graft-versus-host disease (GVHD), which significantly impacts the prognosis of allogeneic hematopoietic stem cell transplantation. However, the lack of an effective strategy for inducing MDSC production in vivo has hindered their clinical application. In our previous study, MDSC expansion was observed in interleukin (IL)-27-treated mice.METHODS:
In this study, we overexpressed exogenous IL-27 in mice using a recombinant adeno-associated virus vector to investigate its therapeutic and exacerbating effects in murine GVHD models.RESULTS:
In our study, we demonstrated that exogenous administration of IL-27 significantly suppressed GVHD development in a mouse model. We found that IL-27 treatment indirectly inhibited the proliferation and activation of donor T cells by rapidly expanding recipient and donor myeloid cells, which act as MDSCs after irradiation or under inflammatory conditions, rather than through regulatory T-cell expansion. Additionally, IL-27 stimulated MDSC expansion by enhancing granulocyte-monocyte progenitor generation. Notably, we verified that IL-27 signaling in donor T cells exerted an antagonistic effect on GVHD prevention and treatment. Further investigation revealed that combination therapy involving IL-27 and T-cell depletion exhibited remarkable preventive effects on GVHD in both mouse and xenogeneic GVHD models.CONCLUSIONS:
Collectively, these findings suggest that IL-27 promotes MDSC generation to reduce the incidence of GVHD, whereas targeted activation of IL-27 signaling in myeloid progenitors or its combination with T-cell depletion represents a potential strategy for GVHD therapy.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Idioma:
En
Revista:
Transplantation
Año:
2024
Tipo del documento:
Article
País de afiliación:
China