普乐沙福
CXCR4型
医学
免疫系统
树突状细胞
T细胞
免疫学
癌症研究
移植
免疫耐受
细胞
生物
内科学
趋化因子
遗传学
作者
Junfen Fu,Christian Lehmann,Xinning Wang,Mandy Wahlbuhl,Ida Allabauer,Benjamin Wilde,Lukas Amon,Sebastian Dolff,R. Cesnjevar,Andreas Kribben,Joachim Woelfle,Wolfgang Rascher,Peter F. Hoyer,Diana Dudziak,Oliver Witzke,André Hoerning
标识
DOI:10.1038/s41598-021-03115-z
摘要
Allograft-specific regulatory T cells (Treg cells) are crucial for long-term graft acceptance after transplantation. Although adoptive Treg cell transfer has been proposed, major challenges include graft-specificity and stability. Thus, there is an unmet need for the direct induction of graft-specific Treg cells. We hypothesized a synergism of the immunotolerogenic effects of rapamycin (mTOR inhibition) and plerixafor (CXCR4 antagonist) for Treg cell induction. Thus, we performed fully-mismatched heart transplantations and found combination treatment to result in prolonged allograft survival. Moreover, fibrosis and myocyte lesions were reduced. Although less CD3+ T cell infiltrated, higher Treg cell numbers were observed. Noteworthy, this was accompanied by a plerixafor-dependent plasmacytoid dendritic cells-(pDCs)-mobilization. Furthermore, in vivo pDC-depletion abrogated the plerixafor-mediated Treg cell number increase and reduced allograft survival. Our pharmacological approach allowed to increase Treg cell numbers due to pDC-mediated immune regulation. Therefore pDCs can be an attractive immunotherapeutic target in addition to plerixafor treatment.
科研通智能强力驱动
Strongly Powered by AbleSci AI