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Myeloid-derived suppressor cells-induced exhaustion of CD8 + T-cell participates in rejection after liver transplantation.

التفاصيل البيبلوغرافية
العنوان: Myeloid-derived suppressor cells-induced exhaustion of CD8 + T-cell participates in rejection after liver transplantation.
المؤلفون: Zhou LX; Liver Transplantation Center, National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, China.; State Key Lab of Digestive Health, Beijing, China., Jiang YZ; Liver Transplantation Center, National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, China.; State Key Lab of Digestive Health, Beijing, China.; Department of Critical Liver Diseases, Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China., Li XQ; Organ Transplantation Center, Affiliated Hospital of Qingdao University, Qingdao, China., Zhang JM; Liver Transplantation Center, National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, China.; State Key Lab of Digestive Health, Beijing, China., Li SP; Department of Hepatopancreaticobiliary Surgery, Henan Provincial People's Hospital, Zhengzhou University, Zhengzhou, China., Wei L; Liver Transplantation Center, National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, China.; State Key Lab of Digestive Health, Beijing, China., Zhang HM; Liver Transplantation Center, National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, China.; State Key Lab of Digestive Health, Beijing, China., Zhou GP; Liver Transplantation Center, National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, China.; State Key Lab of Digestive Health, Beijing, China., Chen XJ; Liver Transplantation Center, National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, China.; State Key Lab of Digestive Health, Beijing, China., Sun LY; Liver Transplantation Center, National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, China.; State Key Lab of Digestive Health, Beijing, China.; Department of Critical Liver Diseases, Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China., Zhu ZJ; Liver Transplantation Center, National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, China. zhu-zhijun@outlook.com.; State Key Lab of Digestive Health, Beijing, China. zhu-zhijun@outlook.com.
المصدر: Cell death & disease [Cell Death Dis] 2024 Jul 16; Vol. 15 (7), pp. 507. Date of Electronic Publication: 2024 Jul 16.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101524092 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-4889 (Electronic) NLM ISO Abbreviation: Cell Death Dis Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London : Nature Pub. Group
مواضيع طبية MeSH: CD8-Positive T-Lymphocytes*/immunology , CD8-Positive T-Lymphocytes*/metabolism , Myeloid-Derived Suppressor Cells*/metabolism , Myeloid-Derived Suppressor Cells*/immunology , Graft Rejection*/immunology , Liver Transplantation* , Mice, Inbred C57BL*, Animals ; Humans ; Mice ; Male ; Middle Aged ; Female ; Adult ; STAT3 Transcription Factor/metabolism ; Programmed Cell Death 1 Receptor/metabolism ; Liver/pathology ; Liver/metabolism
مستخلص: Liver transplantation (LT) rejection remains the most pervasive problem associated with this procedure, while the mechanism involved is still complicated and undefined. One promising solution may involve the use of myeloid-derived suppressor cells (MDSC). However, the immunological mechanisms underlying the effects of MDSC after LT remain unclear. This study is meant to clarify the role MDSCs play after liver transplantation. In this study, we collected liver tissue and peripheral blood mononuclear cells (PBMC) from LT patients showing varying degrees of rejection, as well as liver and spleen tissue samples from mice LT models. These samples were then analyzed using flow cytometry, immunohistochemistry and multiple immunofluorescence. M-MDSCs and CD8 + T-cells extracted from C57/BL6 mice were enriched and cocultured for in vitro experiments. Results, as obtained in both LT patients and LT mice model, revealed that the proportion and frequency of M-MDSC and PD-1 + T-cells increased significantly under conditions associated with a high degree of LT rejection. Within the LT rejection group, our immunofluorescence results showed that a close spatial contiguity was present between PD-1 + T-cells and M-MDSCs in these liver tissue samples and the proportion of CD84/PD-L1 double-positive M-MDSC was greater than that of G-MDSC. There was a positive correlation between the activity of CD84 and immunosuppressive function of M-MDSCs including PD-L1 expression and reactive oxygen species (ROS) production, as demonstrated in our in vitro model. M-MDSCs treated with CD84 protein were able to induce co-cultured CD8 + T-cells to express high levels of exhaustion markers. We found that CD84 regulated M-MDSC function via expression of PD-L1 through activation of the Akt/Stat3 pathway. These results suggest that the capacity for CD84 to regulate M-MDSC induction of CD8 + T-cell exhaustion may play a key role in LT rejection. Such findings provide important, new insights into the mechanisms of tolerance induction in LT.
(© 2024. The Author(s).)
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المشرفين على المادة: 0 (STAT3 Transcription Factor)
0 (Programmed Cell Death 1 Receptor)
تواريخ الأحداث: Date Created: 20240716 Date Completed: 20240716 Latest Revision: 20240716
رمز التحديث: 20240717
DOI: 10.1038/s41419-024-06834-z
PMID: 39013845
قاعدة البيانات: MEDLINE
الوصف
تدمد:2041-4889
DOI:10.1038/s41419-024-06834-z