Complement component 3 deficiency prolongs MHC-II disparate skin allograft survival by increasing the CD4(+) CD25(+) regulatory T cells population
| Autor: | Gui-lian Xu, Yan-bo Lv, Ke-qin Zhang, Ming Tang, Quan-you Zheng, Shen-ju Liang, You Li, Kun Zhang, Gui-qing Li |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
medicine.drug_class medicine.medical_treatment Population chemical and pharmacologic phenomena Biology Monoclonal antibody T-Lymphocytes Regulatory Article 03 medical and health sciences 0302 clinical medicine medicine Animals IL-2 receptor education Cell Proliferation Inflammation education.field_of_study Mice Inbred BALB C Multidisciplinary Complement component 3 Graft Survival Lymphocyte differentiation Histocompatibility Antigens Class II Interleukin-2 Receptor alpha Subunit FOXP3 hemic and immune systems Complement C3 Dendritic Cells Skin Transplantation Th1 Cells Complement system Mice Inbred C57BL 030104 developmental biology surgical procedures operative Immunology CD4 Antigens Th17 Cells Chemokines 030215 immunology Allotransplantation |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | Recent reports suggest that complement system contributes to allograft rejection. However, its underlying mechanism is poorly understood. Herein, we investigate the role of complement component 3 (C3) in a single MHC-II molecule mismatched murine model of allograft rejection using C3 deficient mice (C3−/−) as skin graft donors or recipients. Compared with C3+/+ B6 allografts, C3−/− B6 grafts dramatically prolonged survival in MHC-II molecule mismatched H-2bm12 B6 recipients, indicating that C3 plays a critical role in allograft rejection. Compared with C3+/+ allografts, both Th17 cell infiltration and Th1/Th17 associated cytokine mRNA levels were clearly reduced in C3−/− allografts. Moreover, C3−/− allografts caused attenuated Th1/Th17 responses, but increased CD4+CD25+Foxp3+ regulatory T (Treg) cell expression markedly in local intragraft and H-2bm12 recipients. Depletion of Treg cells by anti-CD25 monoclonal antibody (mAb) negated the survival advantages conferred by C3 deficiency. Our results indicate for the first time that C3 deficiency can prolong MHC-II molecule mismatched skin allograft survival, which is further confirmed to be associated with increased CD4+ CD25+ Treg cell population expansion and attenuated Th1/Th17 response. |
| Databáze: | OpenAIRE |
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