The inhibitory leukocyte immuno-globulin-like receptors (LILRBs) play an important role in innate immunity. Currently, no data exist regarding the role of LILRB4 and LILRB5 in the activation of immune signaling pathways in mammalian and avian species. Here, we report for the first time, the cloning and structural and functional analyses of chicken LILRB4-5 genes identified from 2 genetically disparate chicken lines. Comparison of LILRB4-5 amino acid sequences from lines 6.3 and 7.2 with those of mammalian proteins revealed 17 to 62% and 19 to 29% similarity, respectively. Phylogenetic analysis indicated that the chicken LILRB4-5 genes were closely associated with those of other species. LILRB4-5 could be subdivided into 2 groups having distinct immunoreceptor tyrosine-based inhibitory motifs, which bind to Src homology 2-containing tyrosine phosphatase 2 (SHP-2). Importantly, LILRB4-5 also upregulated the major histocompatibility complex (MHC) class I and β2-microglobulin gene expression as well as the expression of transporter associated with antigen processing 1-2, which play an important role in MHC class I activation. Our results indicate that LILRB4-5 are transcriptional regulators of the MHC class I pathway components and regulate innate immune responses. Furthermore, LILRB4-5 could activate the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway genes in macrophages and induce the expression of chemokines and T helper (Th)1, Th2, and Th17 cytokines. Our data suggest that LILRB4-5 are innate immune receptors associated with SHP-2, MHC class I, and β2-microglobulin. Additionally, they activate the JAK/STAT signaling pathway and control the expression of cytokines in macrophages.

中文翻译：

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新型鸡白细胞免疫球蛋白样受体亚家族 B 成员 4 和 5 的表征和功能分析。

抑制性白细胞免疫球蛋白样受体（LILRBs）在先天免疫中起重要作用。目前，没有关于 LILRB4 和 LILRB5 在激活哺乳动物和鸟类免疫信号通路中的作用的数据。在这里，我们首次报告了从 2 个基因不同的鸡系中鉴定的鸡 LILRB4-5 基因的克隆以及结构和功能分析。来自 6.3 和 7.2 系的 LILRB4-5 氨基酸序列与哺乳动物蛋白质的比较显示分别有 17% 到 62% 和 19% 到 29% 的相似性。系统发育分析表明鸡的LILRB4-5基因与其他物种密切相关。LILRB4-5 可细分为 2 组，具有不同的基于免疫受体酪氨酸的抑制基序，它与含有 Src 同源性 2 的酪氨酸磷酸酶 2 (SHP-2) 结合。重要的是，LILRB4-5 还上调了主要组织相容性复合体 (MHC) I 类和 β2-微球蛋白基因的表达，以及与抗原加工相关的转运蛋白 1-2 的表达，它们在 MHC I 类激活中起重要作用。我们的研究结果表明 LILRB4-5 是 MHC I 类途径成分的转录调节因子并调节先天免疫反应。此外，LILRB4-5 可以激活巨噬细胞中的 Janus 激酶/信号转导和转录激活因子 (JAK/STAT) 信号通路基因，并诱导趋化因子和 T 辅助细胞 (Th)1、Th2 和 Th17 细胞因子的表达。我们的数据表明 LILRB4-5 是与 SHP-2、MHC I 类和 β2-微球蛋白相关的先天免疫受体。此外，