MiR-669b-3p regulates CD4+ T cell function by down-regulating indoleamine-2, 3-dioxygenase

ObjectiveAcute rejection is a major cause of morbidity and mortality after solid organ transplantation. Therefore, optimizing treatment strategies and improving curative effect is urgent and necessary. Reliable biomarkers for acute rejection and the underlying molecular mechanisms remain to be determined.MethodsIn this study, we established a mouse-to-mouse cardiac transplantation model and identified miR-669b-3p as a potential biomarker of acute rejection using a microRNA polymerase chain reaction (PCR)-based chip assay.ResultsFurther analyses showed that miR-669b-3p negatively regulated indoleamine-2,3-dioxygenase (IDO), a rate-limiting enzyme of tryptophan catabolism inhibiting T cell function. Using mixed lymphocyte reaction assay, we showed that miR-669b-3p increased proliferation stimulation index and inhibited apoptosis in CD4⁺ T cells. Moreover, miR-669b-3p regulated the expression of inflammatory cytokines such as tumor necrosis factor alpha (TNF-α) and Interleukin 10 (IL-10) and contributed to cytokine shift towards a Th2-dominant response.ConclusionOur results advance the current understanding of the immune regulatory function of miRNA and shed light on the role of miR-669b-3p in CD4⁺ T cells, suggesting that miR-669b-3p is a potential target for acute allograft rejection.