Mir‐27a‐3p attenuates bronchiolitis obliterans in vivo via the regulation of dendritic cells’ maturation and the suppression of myofibroblasts’ differentiation

Clinical and Translational Medicine

Jun Chen¹  Ming Dong¹  Tong Li¹  Honglin Zhao¹  Xin Wang²  Yi Liu³  Yunwei Yang³  Yaqing Jing³  Jing Wang⁴ 

[1] Department of Lung Cancer Surgery Tianjin Medical University General Hospital Tianjin P. R. China;Department of Pediatric Surgery Tianjin Children's Hospital Tianjin P. R. China;School of Basic Medical Sciences Tianjin Medical University Tianjin P. R. China;Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment Tianjin Lung Cancer Institute Tianjin Medical University General Hospital Tianjin P. R. China;

关键词: bronchiolitis obliterans;    dendritic cells;    lung transplantation;    mir‐27a‐3p;   

DOI  :  10.1002/ctm2.140

来源: DOAJ

【 摘 要 】

Abstract 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‐β level. Furthermore, mir‐27a‐3p regulated TGF‐β function, inhibited TGF‐β/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.

【 授权许可】

Unknown