Differentiation and immunosuppressive function of CD19^(+)CD24^(hi)CD27^(+) regulatory B cells are regulated through the miR-29a-3p/NFAT5 pathway

Background: Regulatory B cells(Bregs) is an indispensable element in inducing immune tolerance after liver transplantation. As one of the microRNAs(miRNAs), mi R-29a-3p also inhibits translation by degrading the target mRNA, and yet the relationship between Bregs and mi R-29a-3p has not yet been fully explored. This study aimed to investigate the impact of miR-29a-3p on the regulation of differentiation and immunosuppressive functions of memory Bregs(m Bregs) and ultimately provide potentially effective therapies in inducing immune tolerance after liver transplantation. Methods: Flow cytometry was employed to determine the levels of Bregs in peripheral blood mononuclear cells. TaqMan low-density array miRNA assays were used to identify the expression of different miRNAs, electroporation transfection was used to induce mi R-29a-3p overexpression and knockdown, and dual luciferase reporter assay was used to verify the target gene of miR-29a-3p. Results: In patients experiencing acute rejection after liver transplantation, the proportions and immunosuppressive function of m Bregs in the circulating blood were significantly impaired. mi R-29a-3p was found to be a regulator of m Bregs differentiation. Inhibition of miR-29a-3p, which targeted nuclear factor of activated T cells 5(NFAT5), resulted in a conspicuous boost in the differentiation and immunosuppressive function of m Bregs. The inhibition of mi R-29a-3p in CD19~+ B cells was capable of raising the expression levels of NFAT5, thereby promoting B cells to differentiate into m Bregs. In addition, the observed enhancement of differentiation and immunosuppressive function of m Bregs upon mi R-29a-3p inhibition was abolished by the knockdown of NFAT5 in B cells. Conclusions: mi R-29a-3p was found to be a crucial regulator for m Bregs differentiation and immunosuppressive function. Silencing mi R-29a-3p could be a potentially effective therapeutic strategy for inducing immune tolerance after liver transplantation.

Successful disintegration,dissolution and drainage of intracholedochal hematoma by percutaneous transhepatic intervention

Hemobilia is a rare biliary complication of liver transplantation.The predominant cause of hemobilia is iatrogenic,and it is often associated with traumatic operations,such as percutaneous liver intervention,endoscopic retrograde cholangiopancreatography,cholecystectomy,biliary tract surgery,and liver transplantation.Percutaneous transhepatic cholangiography and liver biopsy are two major causes of hemobilia in liver transplant recipients.Hemobilia may also be caused by coagulation defects.It can form intracholedochal hematomas,causing obstructive jaundice.Herein we describe a patient with an intracholedochal hematoma resulting in significant obstructive jaundice after liver transplantation for fulminant hepatic failure.Previous studies have shown that percutaneous transhepatic manipulation is a major cause of hemobilia after liver transplantation,but in our case,percutaneous transhepatic intervention was used to relieve the biliary obstruction and dissolve the biliary clot,with a good outcome.