期刊
SCANDINAVIAN JOURNAL OF IMMUNOLOGY
卷 89, 期 4, 页码 -出版社
WILEY
DOI: 10.1111/sji.12750
关键词
heart transplantation; interleukin-35; mesenchymal stem cells; regulatory T cells
类别
资金
- Tianjin Medical University Science Foundation [2014KYM03]
- Natural Science Foundation of Tianjin [18JCYBJC26400]
- National Natural Science Foundation of China for Young Scholars [31400764]
- Tianjin City High School Science & Technology Found Planning Project [20130113]
Interleukin-35 (IL-35) is a cytokine recently discovered to play a potent immunosuppressive role by intensifying the functions of regulatory T cells and inhibiting the proliferation and functions of T helper 1 and T helper 17 cells. Mesenchymal stem cells (MSCs) have recently emerged as promising candidates for cell-based immune therapy, and our previous study showed that IL-35 gene modification can effectively enhance the therapeutic effect of MSCs in vitro. In this study, we isolated adipose tissue-derived MSCs in vitro and infected them with lentiviral vectors overexpressing the IL-35 gene, thereby creating IL-35-MSCs. Subsequently, IL-35-MSCs were then injected into mice of the allogeneic heterotopic abdominal heart transplant model to determine their effect on allograft rejection. The results showed that IL-35-MSCs could continuously secrete IL-35 in vivo and in vitro, successfully alleviate allograft rejection and prolong graft survival. In addition, compared to MSCs, IL-35-MSCs showed a stronger immunosuppressive ability and further reduced the percentage of Th17 cells, increased the proportion of CD4(+) Foxp3(+) T cells, and regulated Th1/Th2 balance in heart transplant mice. These findings suggest that IL-35-MSCs have more advantages than MSCs in inhibiting graft rejection and may thus provide a new approach for inducing immune tolerance during transplantation.
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