Wangkahart Eakapol, Wang Tiehui, Secombes Christopher J
Laboratory of Fish Immunology and Nutrigenomics, Applied Animal and Aquatic Sciences Research Unit, Division of Fisheries, Faculty of Technology, Mahasarakham University, Khamriang Sub-District, Kantarawichai, Mahasarakham, 44150, Thailand; Scottish Fish Immunology Research Centre, School of Biological Sciences, The University of Aberdeen, Aberdeen AB24 2TZ United Kingdom.
Scottish Fish Immunology Research Centre, School of Biological Sciences, The University of Aberdeen, Aberdeen AB24 2TZ United Kingdom.
Fish Shellfish Immunol. 2025 Jan;156:110036. doi: 10.1016/j.fsi.2024.110036. Epub 2024 Nov 19.
Colony-stimulating factor-1 (CSF-1) receptor, also known as macrophage colony-stimulating factor (MCSF) receptor, belongs to the type III protein tyrosine kinase receptor family. MCSF and IL-34 play essential roles in both innate and adaptive immune systems in vertebrates through their shared receptor MCSFR. While the functional study of MCSFR in mammals has been well-demonstrated, its role in fish remains limited. Therefore, this report aims to identify and study the expression of the MCSFR genes in rainbow trout Oncorhynchus mykiss, where four paralogues were found present at different genomic loci, two identified for the first time in this study. The deduced protein structure of these MCSFRs reveals five immunoglobulin (Ig)-like domains, a transmembrane domain and a conserved intracellular domain containing a glycine-rich motif (Gly-x-Gly-x-x-Gly), similar to other species. Phylogenetic and synteny analyses demonstrate that MCSFR are present throughout vertebrates, with two forms present in teleost fish more generally (type I and type II MCSFR), existing as pairs of genes (MCSFR1a/MCSFR1b, MCSFR2a/MCSFR2b) in trout. The MCSFR genes are widely expressed, with higher transcript levels observed in immune tissues such as the spleen, blood and head kidney. The paralogues showed marked differences in expression modulation. Following Yersinia ruckeri infection, MCSFR2a was highly induced but after stimulation of RTS-11 cells, a trout monocyte/macrophage-like cell line, with Y. ruckeri flagellin both MCSFR1b and MCSFR2a were induced. However, none of the different paralogues of MCSFR were induced by proinflammatory cytokines (trout rTNF-α, rIL-6 and rIFN-γ). This study adds to our knowledge of the molecules/pathways present in fish that drive macrophage regulation and activation, and emphasizes the complexity present with multiple ligands and receptors involved.
集落刺激因子-1（CSF-1）受体，也称为巨噬细胞集落刺激因子（MCSF）受体，属于III型蛋白酪氨酸激酶受体家族。MCSF和IL-34通过它们共同的受体MCSFR在脊椎动物的先天性和适应性免疫系统中发挥重要作用。虽然MCSFR在哺乳动物中的功能研究已经得到充分证明，但其在鱼类中的作用仍然有限。因此，本报告旨在鉴定和研究虹鳟Oncorhynchus mykiss中MCSFR基因的表达，在该物种中发现四个旁系同源基因存在于不同的基因组位点，其中两个是本研究首次鉴定的。这些MCSFR推导的蛋白质结构显示有五个免疫球蛋白（Ig）样结构域、一个跨膜结构域和一个保守的细胞内结构域，其中包含一个富含甘氨酸的基序（Gly-x-Gly-x-x-Gly），与其他物种相似。系统发育和共线性分析表明，MCSFR存在于整个脊椎动物中，硬骨鱼中更普遍存在两种形式（I型和II型MCSFR），在鳟鱼中以基因对的形式存在（MCSFR1a/MCSFR1b，MCSFR2a/MCSFR2b）。MCSFR基因广泛表达，在脾脏、血液和头肾等免疫组织中观察到较高的转录水平。旁系同源基因在表达调控上表现出明显差异。感染鲁氏耶尔森菌后，MCSFR2a被高度诱导，但在用鲁氏耶尔森菌鞭毛蛋白刺激虹鳟单核细胞/巨噬细胞样细胞系RTS-11细胞后，MCSFR1b和MCSFR2a均被诱导。然而，促炎细胞因子（虹鳟rTNF-α、rIL-6和rIFN-γ）均未诱导MCSFR的不同旁系同源基因。本研究增加了我们对鱼类中驱动巨噬细胞调节和激活的分子/途径的了解，并强调了涉及多种配体和受体的复杂性。
