Dynamics and MicroRNA144/451-mediated mechanisms of regulatory B Cells during Schistosoma japonicum infection in Mice

초록

Schistosoma japonicum (S. japonicum) infection and soluble egg antigens (SEA) can induce various immune responses, including the generation of IL-10-producing regulatory B cells (Bregs). This study investigated the dynamic changes and induction mechanisms of Bregs during S. japonicum infection. We demonstrated that CD19+IL-10+Bregs and CD19+Tim-1+ Bregs secreting IL-10 gradually increased from 6 to 13 weeks after infection. The CD19+Tim-1+ Bregs exhibited immunosuppressive functions by promoting IL-4 secretion, inhibiting IL-17 production in CD4+ T cells, and increasing the percentages of CD4+CD25+Foxp3+ T cells. MicroRNAs play a key role in both the early differentiation and effector differentiation of B cells in the immune system. We analyzed the expression of miRNAs in the splenic B cells of mice infected with S. japonicum for 13 weeks and predicted their target genes. There were 33 up-regulated and 10 down-regulated miRNAs. Furthermore, we found that Bregs could not be induced in miR-144/451-/- mice after S. japonicum infection and SEA stimulation. The effect of miR-144/451 on Bregs may be mediated through the mTOR signaling pathway. These findings provide new insights into the mechanisms underlying Bregs activation and their role in modulating immune responses during schistosomiasis.

키워드