Pyroptosis,a novel form of inflammation-related programmed cell death that often occurs in myeloid cells,plays an important role in multiple inflammatory diseases.Our previous study revealed macrophage dysfunction in ...Pyroptosis,a novel form of inflammation-related programmed cell death that often occurs in myeloid cells,plays an important role in multiple inflammatory diseases.Our previous study revealed macrophage dysfunction in acute graft-versus-host disease(a GVHD).However,whether macrophages undergo pyroptosis in a GVHD remains unknown.In our study,macrophage pyroptosis was observed in a GVHD mice.Additionally,serum IL-1βand IL-18 levels were increased in a GVHD patients.Almost all peritoneal macrophages in the a GVHD mice were derived from the donors.Less pathological damage and a longer survival time were observed in the mice that received purified T cells and bone marrow(BM)from AAV9-F4/80-GSDMD mice,indicating that macrophage pyroptosis in donor mice promoted the development of a GVHD.In addition,decreased proportions of CD69^(+)CD4^(+)T cells,Th1 cells and Th17 cells and an increased proportion of Tregs were observed in the recipients when GSDMD was suppressed in the donor macrophages.Administration of a pyroptosis inhibitor significantly alleviated the severity of a GVHD without impairing graft-versus-lymphoma(GVL)effects.Our results suggested that donor-derived macrophages undergo pyroptosis in a GVHD,and these cells might participate in the development of a GVHD by affecting the activation and differentiation of CD4^(+)cells.The pyroptosis inhibitor disulfiram is a potentially promising agent for a GVHD treatment.展开更多
基金supported by the National Key Research and Development Program of China(2023YFC2507803)the National Natural Science Foundation of China(82300247,82430006,82230004,82130008)+1 种基金Beijing Natural Science Foundation(L248044,7242154,7232188)Beijing Tongzhou Science and Technology Foundation(CXTD2024005)。
文摘Pyroptosis,a novel form of inflammation-related programmed cell death that often occurs in myeloid cells,plays an important role in multiple inflammatory diseases.Our previous study revealed macrophage dysfunction in acute graft-versus-host disease(a GVHD).However,whether macrophages undergo pyroptosis in a GVHD remains unknown.In our study,macrophage pyroptosis was observed in a GVHD mice.Additionally,serum IL-1βand IL-18 levels were increased in a GVHD patients.Almost all peritoneal macrophages in the a GVHD mice were derived from the donors.Less pathological damage and a longer survival time were observed in the mice that received purified T cells and bone marrow(BM)from AAV9-F4/80-GSDMD mice,indicating that macrophage pyroptosis in donor mice promoted the development of a GVHD.In addition,decreased proportions of CD69^(+)CD4^(+)T cells,Th1 cells and Th17 cells and an increased proportion of Tregs were observed in the recipients when GSDMD was suppressed in the donor macrophages.Administration of a pyroptosis inhibitor significantly alleviated the severity of a GVHD without impairing graft-versus-lymphoma(GVL)effects.Our results suggested that donor-derived macrophages undergo pyroptosis in a GVHD,and these cells might participate in the development of a GVHD by affecting the activation and differentiation of CD4^(+)cells.The pyroptosis inhibitor disulfiram is a potentially promising agent for a GVHD treatment.
