Illawarra Health and Medical Research Institute, Wollongong, NSW, 2522, Australia; Molecular Horizons and School of Chemistry and Molecular Bioscience, University of Wollongong, Wollongong, NSW, 2522, Australia.
Illawarra Health and Medical Research Institute, Wollongong, NSW, 2522, Australia; Molecular Horizons and School of Chemistry and Molecular Bioscience, University of Wollongong, Wollongong, NSW, 2522, Australia.
Curr Opin Pharmacol. 2023 Feb;68:102346. doi: 10.1016/j.coph.2022.102346. Epub 2023 Jan 10.
Allogeneic hematopoietic stem cell transplantation is used to treat blood cancers, but often results in lethal graft-versus-host disease (GVHD). GVHD is an inflammatory disorder mediated by donor leukocytes that damage host tissues. Purinergic signalling plays important roles in GVHD development in mice but studies of these pathways in human GVHD remain limited. P2X7 receptor activation by ATP on host antigen presenting cells contributes to the induction of GVHD, while activation of this receptor on regulatory T cells, myeloid-derived suppressor cells and possibly type 3 innate lymphoid cells results in their loss to promote GVHD progression. In contrast, A receptor activation by adenosine on donor T cells serves to restrict GVHD development. These and other purinergic signalling molecules remain potential biomarkers and therapeutic targets in GVHD.
同种异体造血干细胞移植用于治疗血液癌症，但常导致致命的移植物抗宿主病（GVHD）。GVHD 是一种由供体白细胞介导的炎症性疾病，会损害宿主组织。嘌呤能信号在小鼠 GVHD 的发展中起着重要作用，但对人类 GVHD 中这些途径的研究仍然有限。ATP 对宿主抗原呈递细胞上 P2X7 受体的激活有助于诱导 GVHD，而该受体在调节性 T 细胞、髓源性抑制细胞和可能的 3 型先天淋巴细胞上的激活导致其丧失，从而促进 GVHD 进展。相反，供体 T 细胞上的腺苷对 A 受体的激活有助于限制 GVHD 的发展。这些和其他嘌呤能信号分子仍然是 GVHD 的潜在生物标志物和治疗靶点。
