MicroRNA-7565 negatively regulates the IL-4/13-mediated Th2 immune response by targeting IL-13Rα1 in large yellow...

IL-4 and IL-13 are cytokines with structural homology, exerting critical functions in the Th2 immune response via binding to their respective receptor complexes and activating the MAPK and mTOR pathways. MicroRNAs (miRNAs) modulate diverse molecular processes via suppressing messenger RNA translation or inducing messenger RNA degradation. Although miR-7565 has been previously linked to embryonic development, its regulatory effects on the Th2 immune response remain unknown. In this study, miR-7565 was first identified in large yellow croaker (Larimichthys crocea), which exhibits high conservation across vertebrates. The expression of Lcil-13rα1 is negatively regulated by miR-7565 through its direct binding to the 3'UTR of Lcil-13rα1. MiR-7565 overexpression led to a notable decrease in endogenous Lcil-13rα1 mRNA levels. MiR-7565 overexpression notably suppressed the activation of MEK1/2 and 4E-BP mediated by LcIL-4/13A and LcIL-4/13B. Moreover, miR-7565 weakened the stimulating impacts of LcIL-4/13A and LcIL-4/13B on T cell proliferation/differentiation, and B cell proliferation. These findings indicate that miR-7565 suppresses the signal transduction induced by IL-4/13A and IL-4/13B by targeting Lcil-13rα1, thereby negatively regulating the Th2 immune response. This study advances our knowledge of miRNA-mediated regulatory mechanisms of adaptive immunity in fish.