IL-10-producing B cells attenuate cardiac inflammation by regulating Th1 and Th17 cells in acute viral myocarditis induced by coxsackie virus B3

Aims: This work aimed to evaluate the regulatory function of IL-10-producing B cells in viral myocarditis (VMC). Main methods: We adoptively transferred purified IL-10-producing B cells to VMC mice via the tail vein. We observed the inflammatory responses and cardiac lesions by histological analysis, examined the proportions of spleen Th1 and T17 cells by flow cytometry and expression levels of related transcription factors (T-bet and ROR gamma t) by reverse transcription polymerase chain reaction (RT-PCR), and calculated the cardiac pathological scores and the mean survival times. Key findings: IL-10-producing B cells were found to be T cell-dependent in the pathogenesis of VMC. They mainly downregulated T-bet and ROR.t mRNA levels to decrease the proportions of Th1 and Th17 cells, thereby restraining the inflammation and damage in the myocardium in B cell-deficient VMC mice. Adoptive transfer of IL10-producing B cells before VMC induction also normalized the inflammatory responses and prolonged the survival time in wild-type (WT) VMC mice. While the transfer of IL-10-producing B cells on day 3 of VMC alleviated the severity of disease, it did not extend the mean survival time of VMC mice. By contrast, IL-10-producing B cells showed no effect on day 7 of VMC. In conclusion, IL-10-producing B cells downregulate the proportion of Th1 and Th17 cells to alleviate inflammatory damage in the myocardium during VMC before the induction or the early phase of disease. Significance: These findings suggest that IL-10-producing B cells may be a new therapeutic target for modulating the immune response in VMC.