期刊
CLINICAL AND TRANSLATIONAL MEDICINE
卷 10, 期 4, 页码 -出版社
JOHN WILEY & SONS LTD
DOI: 10.1002/ctm2.140
关键词
bronchiolitis obliterans; dendritic cells; lung transplantation; mir-27a-3p
资金
- National Natural Science Foundation of China [81600073] Funding Source: Medline
- Natural Science Foundation of Tianjin City [18JCYBJC92600] Funding Source: Medline
- Wu Jieping Medical Foundation [320.6750.18157] Funding Source: Medline
- Bethune Ethicon Excellent Surgery Foundation [HZB-20181119-7] Funding Source: Medline
Bronchiolitis obliterans (BO), is a chronic rejection phenotype characterized by chronic small airway fibrous obliteration, hinders the patients who suffer from lung transplanting for surviving longer. Cell-based therapies using dendritic cells (DCs) and T regulatory cells (Tregs) have been developed to regulate allograft rejection, and to induce and maintain immune tolerance. In the present study, the effects of mir-27a-3p on regulating DCs as well as resulting effects on BO attenuation have been investigated. According to our reporter assays, the potential targets of mir-27a-3p were Smad2, sprouty2, and Smad4, respectively. Furthermore, sprouty2 inhibition by mir-27-3p indirectly activated extracellular regulated protein kinases (ERK) and increased IL-10 production in DCs. This led to a positive feedback loop that maintained the immature state of DCs via IL-10/JAK/STAT3 pathway, and caused an increase in Foxp3(+)CD4(+)T cells amount as well as TGF-beta level. Furthermore, mir-27a-3p regulated TGF-beta function, inhibited TGF-beta/Smad pathway, and suppressed myofibroblast differentiation through influencing the function of Smad2 and Smad4. In short, the study indicated the effect of mir-27a-3p on suppressing DC maturation, which implicated the potential clinical application in treating postlung transplant BO.
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