Negative regulation of the IL-4/13-mediated Th2 immune response by microRNA-126b via targeting IL-4Rα1 in large yellow croaker (Larimichthys crocea).

The closely related cytokines Interleukin-4 (IL-4) and IL-13 regulate the Th2 immune response by interacting with their specific receptor complexes. MicroRNAs (miRNAs) modulate various biological pathways through mechanisms that either repress mRNA translation or promote messenger RNA degradation. The miRNA miR-126b is implicated in fish embryonic development. However, its role in regulating the Th2 immune response remains unclear. Here, the mature sequence of miR-126b was identified in large yellow croaker (Larimichthys crocea), which is highly conserved among vertebrates. MiR-126b was confirmed to directly target the 3'-UTR of LcIL-4Rα1. Overexpression of miR-126b in primary head kidney leukocytes (PKLs) resulted in a remarkable reduction of LcIL-4Rα1 mRNA levels. Upon transfection with miR-126b mimics and subsequent stimulation by LcIL-4/13A and LcIL-4/13B proteins, the phosphorylation levels of MEK1/2 and 4E-BP1, which serve as essential components of the MAPK and mTOR cascades, were notably decreased in PKLs. Furthermore, overexpression of miR-126b also attenuated the activation effects of LcIL-4/13A and LcIL-4/13B on both T cell proliferation and differentiation, as well as B cell proliferation. These results indicated that miR-126b regulates the Th2 immune response by targeting IL-4Rα1, thereby disrupting IL-4/13A and IL-4/13B-mediated signal transduction. These findings highlight a crucial regulatory role of miR-126b in the Th2 immunity in teleost fish.