Dysfunctional immunoregulation in human liver allograft rejection associated with compromised galectin-1/CD7 pathway function
العنوان: | Dysfunctional immunoregulation in human liver allograft rejection associated with compromised galectin-1/CD7 pathway function |
---|---|
المؤلفون: | Sidong Wei, Jianping Gong, Yiming Liu, Hao Wu, Jinheng Li, Zuo-jin Liu, Ding Cao, Yakun Wu |
المصدر: | Cell Death & Disease Cell Death and Disease, Vol 9, Iss 3, Pp 1-13 (2018) |
بيانات النشر: | Nature Publishing Group UK, 2018. |
سنة النشر: | 2018 |
مصطلحات موضوعية: | 0301 basic medicine, Adult, CD4-Positive T-Lymphocytes, Graft Rejection, Male, Cancer Research, Carcinoma, Hepatocellular, Galectin 1, medicine.medical_treatment, Immunology, Cell, Apoptosis, Antigens, CD7, 030230 surgery, Liver transplantation, T-Lymphocytes, Regulatory, Article, 03 medical and health sciences, Cellular and Molecular Neuroscience, Young Adult, 0302 clinical medicine, Antigen, Downregulation and upregulation, hemic and lymphatic diseases, medicine, Gene silencing, Humans, lcsh:QH573-671, Aged, CD43, Leukosialin, business.industry, lcsh:Cytology, Liver Neoplasms, Cell Biology, Middle Aged, Allografts, Liver Transplantation, carbohydrates (lipids), 030104 developmental biology, medicine.anatomical_structure, Liver, Galectin-1, Female, business |
الوصف: | Regulatory T cells in rejected allograft patients display an inability to control responder T cells. Galectin-1 (Gal1) inhibits responder T cells through binding CD7. We investigated whether the dysfunctional immunoregulation in liver allograft rejection patients results from reduced regulatory T-cell Gal1 expression and/or responder T-cell CD7 expression. Circulating regulatory T cells and responder T cells were profiled from 31 acute rejection transplant patients, 85 transplant patients in remission, and 40 healthy controls. CD7+ and CD7− responder T cells were co-cultured with regulatory T cells to assess regulatory T-cell suppressor function. Gal1-small interfering RNA was used to silence regulatory T-cell Gal1. The CD7+ cell percentage was inversely correlated with AST, ALT, and GGT levels. The proportions of CD7+ responder T cells and Gal1+ regulatory T cells were higher in healthy controls than in transplant patients in remission and lowest in acute rejection transplant patients. Notably, CD7+ responder T-cell susceptibility to Gal1+ regulatory T-cell control was ranked in the same manner. Silencing Gal1 expression in regulatory T cells reduced their ability to suppress CD7+ (but not CD7−) responder T cells. Additionally, the proportions of CD43+ and CD45+ responder T cells were higher in healthy controls than in acute rejection transplant patients. CD43 co-expression (but not CD45 co-expression) on CD7+ responder T cells promoted their apoptosis in a Gal1-dependent manner. In sum, dysfunctional immunoregulation in liver allograft rejection patients can be partly attributed to reduced regulatory T-cell Gal1 expression and reduced responder T-cell CD7 expression. Responder T-cell CD43 downregulation in acute rejection patients may further contribute to reduced responder T-cell responsiveness to regulatory T-cell control. |
اللغة: | English |
تدمد: | 2041-4889 |
الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fb889e77245109b8d7ebfea97089ae8fTest http://europepmc.org/articles/PMC5833641Test |
حقوق: | OPEN |
رقم الانضمام: | edsair.doi.dedup.....fb889e77245109b8d7ebfea97089ae8f |
قاعدة البيانات: | OpenAIRE |
تدمد: | 20414889 |
---|