S1PR5 regulates NK cell responses in preventing graft‐versus‐host disease while preserving graft‐versus‐tumour activity in a murine allogeneic haematopoietic stem cell transplantation model
Autor: | Nan Yang, Xiao-Li Zhao, Tong Liu, Shu Fang, Zhenyang Gu, Lan Luo, Chengying Zhu, Feiyan Wang, Shasha Zhao, Meng Li, Li Wang, Lili Wang, Li-Xun Guan, Chun-Ji Gao |
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Rok vydání: | 2019 |
Předmět: |
Cancer Research
CD3 Cell Graft vs Host Disease CD8-Positive T-Lymphocytes Mice 03 medical and health sciences 0302 clinical medicine Animals Transplantation Homologous Medicine Mice Inbred BALB C biology business.industry Graft vs Tumor Effect Hematopoietic Stem Cell Transplantation Hematology General Medicine medicine.disease Killer Cells Natural Mice Inbred C57BL Transplantation Disease Models Animal Receptors Lysosphingolipid Haematopoiesis surgical procedures operative Graft-versus-host disease medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Cancer research biology.protein Bone marrow Stem cell business CD8 030215 immunology |
Zdroj: | Hematological Oncology. 38:89-102 |
ISSN: | 1099-1069 0278-0232 |
Popis: | Graft-versus-host disease (GVHD) remains a major complication following allogeneic haematopoietic stem cell transplantation (allo-HSCT) leading to high transplant-related mortality. Natural killer (NK) cells have been found to mitigate GVHD without attenuating the graft-versus-tumour (GVT) activity in the murine model of haematopoietic stem cell transplantation. Sphingosine-1-phosphate receptor 5 (S1PR5) is a very important chemokine receptor on NK cells that governs NK cell distribution in vivo and trafficking at lesion sites. Our preliminary studies showed that the incidence of GVHD was negatively correlated with S1PR5 expression in the NK cells of patients after allo-HSCT. In the present study, we found that S1PR5 deficiency in murine NK cells blocked the migration of NK cells from the bone marrow to the GVHD target organs and attenuated the inhibitory effects on the alloreactive T cells, especially CD3+ CD8+ T cells, which may be the reason why the loss of S1PR5 in NK cells could aggravate GVHD in recipient mice. Furthermore, we also demonstrated that the absence of S1PR5 expression in NK cells did not interfere with the antitumour effects of NK cells and T cells in vivo. Taken together, our data indicate that S1PR5 plays an essential role in balancing GVHD and GVT activity. |
Databáze: | OpenAIRE |
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