Development of the LYVE-1 gene with an acidic-amino-acid-rich (AAAR) domain in evolution is associated with acquisition of lymph nodes and efficient adaptive immunity.
Development of the LYVE-1 gene with an acidic-amino-acid-rich (AAAR) domain in evolution is associated with acquisition of lymph nodes and efficient adaptive immunity.
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用酸性氨基酸（AAAR）结构域在进化中开发Lyve-1基因与淋巴结的获取和有效的适应性免疫有关。
DOI：
10.1002/jcp.26159
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发表时间：
2018-04
影响因子：
5.6
通讯作者：
Huang JS
中科院分区：
文献类型：
--
作者：
Huang SS;Li YW;Wu JL;Johnson FE;Huang JS
CRSBP-1(哺乳动物LYVE-1)是一种在淋巴管内皮细胞(LECs)中高表达的膜糖蛋白。它有多个配体，包括透明质酸(HA)和含有CRS基序(碱性氨基酸残基簇)的生长因子/细胞因子(如PDGF-BB和VEGF-A)。配体结合活性分别由连接模块和富含酸性氨基酸(AAAR)结构域介导。这些CRSBP-1/LYVE-1配体已被证明能在LEC单层和野生型小鼠的淋巴管中诱导淋巴管连接的开放。我们假设CRSBP-1/LYVE-1配体，特别是含有CRS的生长因子/细胞因子，在获得性免疫反应和淋巴转移过程中由免疫细胞和癌细胞分泌，用于淋巴进入。我们探讨了Lyve-1的Link模块和aaar结构域在进化过程中的起源及其与淋巴结发育和有效获得性免疫的关系。在进化方面，尤其是对哺乳动物和鸟类来说，淋巴结是适应性免疫系统最近唯一的重大创新。在这里，我们证明了带有aaar结构域的Lyve-1基因在进化中的发展与淋巴结的获得和获得性免疫有关。来自其他没有淋巴结的物种的Lyve-1缺乏aaar结构域和有效的获得性免疫。人工合成的CRSBP-1配体PDGF和VEGF肽分别含有PDGF-BB和VEGFA的CRS基序，它们与CRSBP-1特异结合，但不与PDGFβR或VEGFR2相互作用。这些多肽通过增强伪狂犬病病毒(PRV)疫苗对猪的获得性免疫而发挥佐剂作用。这些结果支持LYVE-1参与哺乳动物获得性免疫的观点。
CRSBP-1 (mammalian LYVE-1) is a membrane glycoprotein highly expressed in lymphatic endothelial cells (LECs). It has multiple ligands, including hyaluronic acid (HA) and growth factors/cytokines (e.g., PDGF-BB and VEGF-A) containing CRS motifs (clusters of basic amino-acid residues). The ligand binding activities are mediated by Link module and acidic-amino-acid-rich (AAAR) domains, respectively. These CRSBP-1/LYVE-1 ligands have been shown to induce opening of lymphatic intercellular junctions in LEC monolayers and in lymphatic vessels in wild-type mice. We hypothesize that CRSBP-1/LYVE-1 ligands, particularly CRS-containing growth factors/cytokines, are secreted by immune and cancer cells for lymphatic entry during adaptive immune responses and lymphatic metastasis. We have looked into the origin of the Link module and AAAR domain of LYVE-1 in evolution and its association with the development of lymph nodes and efficient adaptive immunity. Lymph nodes represent the only major recent innovation of the adaptive immune systems in evolution particularly to mammals and bird. Here we demonstrate that the development of the LYVE-1 gene with the AAAR domain in evolution is associated with acquisition of lymph nodes and adaptive immunity. LYVE-1 from other species, which have no lymph nodes, lack the AAAR domain and efficient adaptive immunity. Synthetic CRSBP-1 ligands PDGF and VEGF peptides, which contain the CRS motifs of PDGF-BB and VEGF-A, respectively, specifically bind to CRSBP-1 but do not interact with either PDGFβR or VEGFR2. These peptides function as adjuvants by enhancing adaptive immunity of pseudorabies virus (PRV) vaccine in pigs. These results support the notion that LYVE-1 is involved in adaptive immunity in mammals.
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