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Negative regulation of the IL-4/13-mediated Th2 immune response by microRNA-126b via targeting IL-4Rα1 in large
Jiamei Liu1, Huazhi Chen1, Wenxing Li1
1College of Marine Sciences, State Key Laboratory of Mariculture Breeding, Key Laboratory of Marine Biotechnology of Fujian Province, College of Life Science, Fujian Agriculture and Forestry University, Fuzhou, 350002, China.
Abstract:
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.
Insights
MicroRNA miR-126b regulates the fish Th2 immune response by targeting Interleukin-4 receptor alpha 1 (IL-4Rα1). This study reveals miR-126b
Area of Science:
- Immunology
- Molecular Biology
- Marine Biology
Background:
- Interleukin-4 (IL-4) and IL-13 are key regulators of the Th2 immune response.
- MicroRNAs (miRNAs) are small non-coding RNAs that modulate gene expression.
- The role of miR-126b in Th2 immunity is not well understood.
Purpose of the Study:
- To investigate the function of miR-126b in the Th2 immune response of large yellow croaker (Larimichthys crocea).
- To identify the target gene of miR-126b involved in the Th2 pathway.
Main Methods:
- Identification and characterization of miR-126b in large yellow croaker.
- Luciferase reporter assay to confirm direct targeting of LcIL-4Rα1 by miR-126b.
- Overexpression of miR-126b in primary head kidney leukocytes (PKLs) and assessment of downstream signaling pathways (MAPK, mTOR) and immune cell responses.
Main Results:
- MiR-126b directly targets the 3'-UTR of LcIL-4Rα1.
- Overexpression of miR-126b reduced LcIL-4Rα1 mRNA levels in PKLs.
- MiR-126b suppressed IL-4/13-mediated signaling, including MEK1/2 and 4E-BP1 phosphorylation, and attenuated T and B cell proliferation and differentiation.
Conclusions:
- MiR-126b plays a significant role in regulating the Th2 immune response in teleost fish.
- MiR-126b exerts its regulatory function by targeting LcIL-4Rα1 and inhibiting IL-4/13 signaling pathways.
- These findings provide new insights into the molecular mechanisms of fish immunity.
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