State Key Laboratory of Estuarine and Coastal Research, School of Life Sciences, East China Normal University, Shanghai, 200241, China.
State Key Laboratory of Estuarine and Coastal Research, School of Life Sciences, East China Normal University, Shanghai, 200241, China.
Fish Shellfish Immunol. 2021 Jun;113:51-60. doi: 10.1016/j.fsi.2021.03.016. Epub 2021 Mar 31.
Killer cell lectin-like receptor G subfamily 1 (KLRG1) is a receptor generally expressed on effector CD8 T cells or NK cells at terminal differentiation stage, and it will be highly induced for lymphocyte cytotoxicity upon pathogen infection or lymphocyte activation. However, little is known about the character or function of KLRG1 in lower vertebrates. In present study, we reappraised a molecule that previously defined as KLRG1 in the genomic sequence of Nile tilapia Oreochromis niloticus, and identified it as an atypical KLRG1-like molecule (defined as On-KLRG1-L), and illustrated its potential function serving as a marker representing effector T lymphocytes of fish species. On-KLRG1-L consists of two C-type lectin-like domains (CTLDs) without transmembrane region, and the tertiary structure of the CTLD is highly alike to that in mouse KLRG1. As a CTLD-containing protein, the recombinant On-KLRG1-L could bind PGN and several microbes in vitro. On-KLRG1-L was widely expressed in immune-associated tissues, with the highest expression level in the gill. Once Nile tilapia is infected by Aeromonas hydrophila, mRNA level of On-KLRG1-L in spleen lymphocytes were significantly up-regulated on 5 days after infection. Meanwhile, On-KLRG1-L protein was also induced on 5 or 8 days after A. hydrophila infection. Furthermore, we found both mRNA and protein levels of On-KLRG1-L were dramatically enhanced within several hours after spleen lymphocytes were activated by T cell-specific mitogen PHA in vitro. More importantly, the ratio of On-KLRG1-L T cells was also augmented after PHA stimulation. The observations suggested that the KLRG1-like molecule from Nile tilapia participated in lymphocyte activation and anti-bacterial adaptive immune response, and could serve as an activation marker of T lymphocytes. Our study thus provided new evidences to understand lymphocyte-mediated adaptive immunity of teleost.
杀伤细胞凝集素样受体 G 亚家族 1(KLRG1)是一种通常在效应 CD8 T 细胞或 NK 细胞的终末分化阶段表达的受体,在病原体感染或淋巴细胞激活时,其对淋巴细胞细胞毒性的诱导作用会显著增强。然而,关于 KLRG1 在低等脊椎动物中的特征或功能知之甚少。在本研究中,我们重新评估了尼罗罗非鱼 Oreochromis niloticus 基因组序列中先前定义为 KLRG1 的分子,并将其鉴定为一种非典型的 KLRG1 样分子(定义为 On-KLRG1-L),并说明了其作为鱼类效应 T 淋巴细胞标志物的潜在功能。On-KLRG1-L 由两个不含跨膜区的 C 型凝集素样结构域(CTLDs)组成,其 CTLD 的三级结构与小鼠 KLRG1 非常相似。作为一种含有 CTLD 的蛋白质,重组 On-KLRG1-L 可以在体外结合 PGN 和几种微生物。On-KLRG1-L 在免疫相关组织中广泛表达,在鳃中表达水平最高。一旦尼罗罗非鱼感染嗜水气单胞菌,感染后第 5 天脾淋巴细胞中 On-KLRG1-L 的 mRNA 水平显著上调。同时,感染嗜水气单胞菌后第 5 天或第 8 天也诱导了 On-KLRG1-L 蛋白的表达。此外,我们还发现脾淋巴细胞经 T 细胞特异性有丝分裂原 PHA 体外激活后数小时内,On-KLRG1-L 的 mRNA 和蛋白水平均显著增强。更重要的是,PHA 刺激后 On-KLRG1-L T 细胞的比例也增加了。这些观察结果表明,来自尼罗罗非鱼的 KLRG1 样分子参与了淋巴细胞的激活和抗细菌适应性免疫反应,并可作为 T 淋巴细胞的激活标志物。我们的研究为理解硬骨鱼类的淋巴细胞介导的适应性免疫提供了新的证据。