College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, 450046, China; Henan Key Laboratory for Innovation and Utilization of Chicken Germplasm Resources, Zhengzhou, 450046, China.
College of Animal Science, South China Agricultural University, Guangzhou, 510642, China.
Dev Comp Immunol. 2024 Jul;156:105159. doi: 10.1016/j.dci.2024.105159. Epub 2024 Mar 15.
Stress-induced immunosuppression (SIIS) is one of the common problems in intensive poultry production, which brings enormous economic losses to the poultry industry. Accumulating evidence has shown that microRNAs (miRNAs) were important regulators of gene expression in the immune system. However, the miRNA-mediated molecular mechanisms underlying SIIS in chickens are still poorly understood. This study aimed to investigate the biological functions and regulatory mechanism of miRNAs in chicken SIIS. A stress-induced immunosuppression model was successfully established via daily injection of dexamethasone and analyzed miRNA expression in spleen. Seventy-four differentially expressed miRNAs (DEMs) was identified, and 229 target genes of the DEMs were predicted. Functional enrichment analysis the target genes revealed pathways related to immunity, such as MAPK signaling pathway and FoxO signaling pathway. The candidate miRNA, gga-miR-146a-5p, was found to be significantly downregulated in the Dex-induced chicken spleen, and we found that Dex stimulation significantly inhibited the expression of gga-miR-146a-5p in Chicken macrophages (HD11). Flow cytometry, 5-ethynyl-2'-deoxyuridine (EdU), cell counting kit-8 (CCK-8) and other assays indicated that gga-miR-146a-5p can promote the proliferation and inhibit apoptosis of HD11 cells. A dual-luciferase reporter assay suggested that the Interleukin 1 receptor associated kinase 2 (IRAK2) gene, which encoded a transcriptional factor, was a direct target of gga-miR-146a-5p, gga-miR-146a-5p suppressed the post-transcriptional activity of IRAK2. These findings not only improve our understanding of the specific functions of miRNAs in avian stress but also provide potential targets for genetic improvement of stress resistance in poultry.
应激诱导的免疫抑制（SIIS）是集约化家禽生产中的常见问题之一，给家禽业带来了巨大的经济损失。越来越多的证据表明，microRNAs（miRNAs）是免疫系统中基因表达的重要调节因子。然而，miRNAs 介导的鸡 SIIS 的分子机制仍知之甚少。本研究旨在探讨 miRNAs 在鸡 SIIS 中的生物学功能和调控机制。通过每日注射地塞米松成功建立了应激诱导的免疫抑制模型，并分析了脾脏中的 miRNA 表达。鉴定出 74 个差异表达的 miRNAs（DEMs），并预测了 DEMs 的 229 个靶基因。靶基因的功能富集分析揭示了与免疫相关的途径，如 MAPK 信号通路和 FoxO 信号通路。候选 miRNA，gga-miR-146a-5p，在 Dex 诱导的鸡脾脏中显著下调，我们发现 Dex 刺激显著抑制了 Chicken macrophages（HD11）中 gga-miR-146a-5p 的表达。流式细胞术、5-乙炔基-2'-脱氧尿苷（EdU）、细胞计数试剂盒-8（CCK-8）等检测表明，gga-miR-146a-5p 可促进 HD11 细胞的增殖并抑制其凋亡。双荧光素酶报告基因实验表明，编码转录因子的白细胞介素 1 受体相关激酶 2（IRAK2）基因是 gga-miR-146a-5p 的直接靶基因，gga-miR-146a-5p 抑制了 IRAK2 的转录后活性。这些发现不仅提高了我们对禽类应激中 miRNAs 特定功能的理解，还为家禽应激抗性的遗传改良提供了潜在的靶标。
