Key Laboratory of Marine Biotechnology of Fujian Province, Institute of Oceanology, College of Life Science, Fujian Agriculture and Forestry University, Fuzhou, 350002, China.
Key Laboratory of Marine Biotechnology of Fujian Province, Institute of Oceanology, College of Life Science, Fujian Agriculture and Forestry University, Fuzhou, 350002, China.
Fish Shellfish Immunol. 2022 Jan;120:45-55. doi: 10.1016/j.fsi.2021.11.007. Epub 2021 Nov 11.
Interleukin (IL)-4 and IL-13 are closely related class I cytokines that play key roles in the T helper (Th)-2 immune response via heterodimeric receptors. IL-4 signals via both the type I (IL-4Rα/γc) and type II (IL-4Rα/IL-13Rα1) receptor complexes, while IL-13 signals only via the type II receptor complex. IL-13Rα2 is traditionally considered a "decoy" receptor for IL-13. However, the IL-4/13 system and its response to pathogenic infection are still not fully understood in fish. In this study, we identified four IL-4/13 receptor subunit genes in the large yellow croaker (Larimichthys crocea): LcIL-4Rα1, LcIL-4Rα2, LcIL-13Rα1, and LcIL-13Rα2. Sequence analysis showed that these receptors possessed typical characteristic domains, including a signal peptide, two fibronectin type III (FN III)-like domains, and a transmembrane domain, but their cytoplasmic regions were not well conserved. The mRNA and protein of the four IL-4/13 receptors were constitutively expressed in all examined tissues of large yellow croaker. Their mRNAs were also detected in primary head kidney macrophages (PKMs), primary head kidney granulocytes (PKGs), and primary head kidney lymphocytes (PKLs). Immunofluorescence assay further showed that LcIL-4Rα and LcIL-13Rα1 were expressed on the membrane of IgM B cells. After stimulation by Vibrio alginolyticus and poly (I:C) (a viral dsRNA mimic), the mRNA levels of LcIL-4/13 receptors were significantly upregulated in the head kidney and spleen. Their mRNA levels were also upregulated in head kidney leukocytes in response to poly (I:C) and lipopolysaccharide (LPS) treatment. Moreover, both recombinant LcIL-4/13A and LcIL-4/13B upregulated LcIL-4Rα1 and LcIL-4Rα2 in primary leukocytes, but only recombinant LcIL-4/13A upregulated LcIL-13Rα1 and LcIL-13Rα2. These results indicated that LcIL-4/13 receptors, containing conserved functional domains, may be involved in the IL-4/13-mediated immune response to pathogenic infections in the large yellow croaker.
白细胞介素 (IL)-4 和 IL-13 是密切相关的 I 类细胞因子，通过异二聚体受体在辅助性 T 细胞 (Th)-2 免疫反应中发挥关键作用。IL-4 通过 I 型 (IL-4Rα/γc) 和 II 型 (IL-4Rα/IL-13Rα1) 受体复合物发出信号，而 IL-13 仅通过 II 型受体复合物发出信号。IL-13Rα2 传统上被认为是 IL-13 的“诱饵”受体。然而，鱼类中的 IL-4/13 系统及其对致病感染的反应仍未完全了解。在这项研究中，我们在大黄鱼 (Larimichthys crocea) 中鉴定了四个 IL-4/13 受体亚基基因：LcIL-4Rα1、LcIL-4Rα2、LcIL-13Rα1 和 LcIL-13Rα2。序列分析表明，这些受体具有典型的特征结构域，包括信号肽、两个纤维连接蛋白 III (FN III)-样结构域和一个跨膜结构域，但它们的细胞质区域没有很好地保守。这四个 IL-4/13 受体的 mRNA 和蛋白在大黄鱼所有检查的组织中均持续表达。它们的 mRNA 也在原头肾巨噬细胞 (PKM)、原头肾粒细胞 (PKG) 和原头肾淋巴细胞 (PKL) 中检测到。免疫荧光检测进一步表明，LcIL-4Rα 和 LcIL-13Rα1 表达在 IgM B 细胞的膜上。在受到溶藻弧菌和聚 (I:C)（一种病毒双链 RNA 模拟物）刺激后，头肾和脾脏中 LcIL-4/13 受体的 mRNA 水平显著上调。头肾白细胞对聚 (I:C) 和脂多糖 (LPS) 处理的反应也导致其 mRNA 水平上调。此外，重组 LcIL-4/13A 和 LcIL-4/13B 上调了原代白细胞中的 LcIL-4Rα1 和 LcIL-4Rα2，但只有重组 LcIL-4/13A 上调了 LcIL-13Rα1 和 LcIL-13Rα2。这些结果表明，含有保守功能结构域的 LcIL-4/13 受体可能参与大黄鱼对致病感染的 IL-4/13 介导的免疫反应。
