Gut microbes enlarged the protective effect of transplanted regulatory B cells on rejection of cardiac allografts
| Autor: | Yufei Fu, Dimin Wang, Hongfei Xu, Renyuan Li, Weidong Li, Aixia Liu, Liang Ma, Lei Guo, Haige Zhao, Peng Teng, Yu Zou, Rongcai Yue, Jingya Fan, Xingjie Xu, Chengyao Ni, Zhen Wang, Xin Chen |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Graft Rejection
Pulmonary and Respiratory Medicine Adoptive cell transfer medicine.medical_treatment Regulatory B cells CD19 Mice Animals Medicine CD40 Antigens TNF Receptor-Associated Factor 6 Heart transplantation B-Lymphocytes Regulatory Mice Inbred BALB C Transplantation CD40 biology business.industry Cyclin-Dependent Kinase 4 Cyclin-Dependent Kinase 6 Dendritic Cells medicine.disease Adoptive Transfer Gastrointestinal Microbiome Transplant rejection Mice Inbred C57BL Disease Models Animal biology.protein Cancer research Heart Transplantation Female Transplantation Tolerance Surgery Tumor necrosis factor alpha Cardiology and Cardiovascular Medicine business Signal Transduction |
| Zdroj: | The Journal of Heart and Lung Transplantation. 40:1502-1516 |
| ISSN: | 1053-2498 |
| DOI: | 10.1016/j.healun.2021.08.008 |
| Popis: | Background Regulatory B cells (Bregs) play an important role in maintaining immune homeostasis and have the potential to induce tolerance. Previous work has found that Breg cells are involved in heart transplantation tolerance. However, the effect of Breg on the transplantation tolerance and the underlying mechanisms remain to be clarified. Methods Using a within-species heart transplantation model, we aimed to investigate the role of CD19+CD5+CD1dhigh Bregs isolated from transplanted mice in preventing transplant rejection in vivo. We also explored the effects of CD40 and tumor necrosis factor receptor-associated factor 6 (TRAF6) ubiquitin ligase on Breg-mediated prolongation of survival in heart transplant (HT) mice, and the regulatory effects of downstream Cdk4 and Cdk6 proteins on dendritic cells (DCs), which clarified the function and molecular mechanism of Breg cells in HT mice. Results Our data suggest that adoptive transfer of the transplanted Bregs served as an effective tolerance-inducing mechanism in HT mice and was involved in the CD40-TRAF6 signaling pathway in DCs. Moreover, DCs collected from the Breg treated HT mice also prolonged the survival of HT mice. Furthermore, DC-specific knockout of TRAF6 diminished Breg-mediated prolongation of survival in HT mice. Interestingly, gut microbes from donors increased the survival of cardiac allografts both in both the absence and presence of Bregs but were not implicated in CD40-TRAF6 signaling. Conclusions These findings reveal a role of Breg cells in the induction of transplantation tolerance through the blockade of the CD40-TRAF6 signaling pathway, which might be used in the treatment of HT in the clinic. |
| Databáze: | OpenAIRE |
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