Differential expression, modulation and bioactivity of distinct fish IL-12 isoforms: implication towards the evolution of Th1-like immune responses.
Differential expression, modulation and bioactivity of distinct fish IL-12 isoforms: implication towards the evolution of Th1-like immune responses.
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不同鱼类 IL-12 亚型的差异表达、调节和生物活性：对 Th1 样免疫反应进化的影响。
DOI：
10.1002/eji.201344273
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发表时间：
2014
影响因子：
5.4
通讯作者：
Wang T
中科院分区：
文献类型：
--
作者：
Wang T
IL-12是由α链（p35）和β链（p40）组成的异二聚体细胞因子。由APC产生的IL-12诱导T、B和NK细胞中的IFN-γ产生。IL-12驱动Th 1细胞分化和IFN-γ分泌，以促进细胞介导的免疫力，这对于防御细胞内病原体至关重要。IL-12在Th 1应答中的重要性与其通过逃避细胞介导的免疫的细胞内病原体的靶向抑制相呼应。最近在鱼类中发现了IL-12亚基，尽管报道的生物活性仅限于高等脊椎动物。在这里，我们报告了p35基因和两个不同的p40基因（p40 b和p40 c）的克隆，能够在虹鳟鱼中产生两种功能性IL-12亚型（p35/p40 b和p35/p40 c）。鳟鱼IL-12亚型在诱导IFN-γ、IL-10和p40 c表达方面具有不同的生物活性。鳟鱼IL-12亚型在体内差异表达和调节，在细菌、病毒和寄生虫感染模型中以及体外刺激的巨噬细胞和白细胞培养物中表现出特异性基因表达谱。这些数据意味着鱼类中可能存在替代或额外的病原体特异性Th样细胞群。这项研究将有助于更广泛地了解低等脊椎动物中驱动宿主-病原体相互作用和Th 1样免疫反应的进化过程。
IL‐12 is a heterodimeric cytokine composed of an α‐chain (p35) and a β‐chain (p40). Primarily produced by APCs, IL‐12 induces IFN‐γ production in T, B and NK cells. IL‐12 drives Th1‐cell differentiation and IFN‐γ secretion to promote cell‐mediated immunity, which is essential in the defence against intracellular pathogens. The importance of IL‐12 in Th1 responses is echoed by its targeted suppression by intracellular pathogens evading cell‐mediated immunity. IL‐12 subunits have been identified recently in fish, although reported bioactivities are limited to higher vertebrates. Here, we report the cloning of a p35 gene and two divergent p40 genes (p40b and p40c), capable of producing two functional IL‐12 isoforms (p35/p40b and p35/p40c) in rainbow trout. Trout IL‐12 isoforms possess distinct bioactivities with respect to the induction of IFN‐γ, IL‐10 and p40c expression. Trout IL‐12 isoforms are differentially expressed and modulated in vivo, exhibiting specific gene expression profiles in bacterial, viral and parasitic infection models, and in vitro in stimulated macrophage and leucocyte cultures. These data imply that alternative or additional pathogen‐specific Th‐like cell populations may exist in fish. This study will facilitate a broader understanding of the evolutionary processes driving host–pathogen interactions and Th1‐like immune responses in lower vertebrates.