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Zebrafish IL-4–like Cytokines and IL-10 Suppress Inflammation but Only IL-10 Is Essential for Gill Homeostasis
The Journal of Immunology ( IF 4.4 ) Pub Date : 2020-07-08 , DOI: 10.4049/jimmunol.2000372
Federica Bottiglione 1 , Christopher T Dee 1 , Robert Lea 1 , Leo A H Zeef 1 , Andrew P Badrock 1 , Madina Wane 2 , Laurence Bugeon 2 , Margaret J Dallman 2 , Judith E Allen 1 , Adam F L Hurlstone 3
Affiliation  

Key Points Zebrafish IL-4–like cytokines promote type 2 and suppress type 1 immunity. Zebrafish IL-10 is potently anti-inflammatory and essential for gill homeostasis. Mucosal surfaces such as fish gills interface between the organism and the external environment and as such are major sites of foreign Ag encounter. In the gills, the balance between inflammatory responses to waterborne pathogens and regulatory responses toward commensal microbes is critical for effective barrier function and overall fish health. In mammals, IL-4 and IL-13 in concert with IL-10 are essential for balancing immune responses to pathogens and suppressing inflammation. Although considerable progress has been made in the field of fish immunology in recent years, whether the fish counterparts of these key mammalian cytokines perform similar roles is still an open question. In this study, we have generated IL-4/13A and IL-4/13B mutant zebrafish (Danio rerio) and, together with an existing IL-10 mutant line, characterized the consequences of loss of function of these cytokines. We demonstrate that IL-4/13A and IL-4/13B are required for the maintenance of a Th2-like phenotype in the gills and the suppression of type 1 immune responses. As in mammals, IL-10 appears to have a more striking anti-inflammatory function than IL-4–like cytokines and is essential for gill homeostasis. Thus, both IL-4/13 and IL-10 paralogs in zebrafish exhibit aspects of conserved function with their mammalian counterparts.

中文翻译:

斑马鱼 IL-4 样细胞因子和 IL-10 抑制炎症,但只有 IL-10 对鳃内稳态至关重要

要点 斑马鱼 IL-4 样细胞因子促进 2 型免疫并抑制 1 型免疫。斑马鱼 IL-10 具有强效抗炎作用,对鳃内稳态至关重要。生物体与外部环境之间的黏膜表面(例如鱼鳃)是接触外来抗原的主要场所。在鳃中,对水传播病原体的炎症反应和对共生微生物的调节反应之间的平衡对于有效的屏障功能和整体鱼类健康至关重要。在哺乳动物中,IL-4 和 IL-13 与 IL-10 协同作用对于平衡对病原体的免疫反应和抑制炎症至关重要。尽管近年来鱼类免疫学领域取得了相当大的进展,但这些关键哺乳动物细胞因子的鱼类对应物是否发挥相似作用仍然是一个悬而未决的问题。在这项研究中,我们生成了 IL-4/13A 和 IL-4/13B 突变斑马鱼 (Danio rerio),并与现有的 IL-10 突变系一起,表征了这些细胞因子功能丧失的后果。我们证明 IL-4/13A 和 IL-4/13B 是维持鳃中 Th2 样表型和抑制 1 型免疫反应所必需的。与哺乳动物一样,IL-10 似乎比 IL-4 样细胞因子具有更显着的抗炎功能,并且对于鳃内稳态至关重要。因此,斑马鱼中的 IL-4/13 和 IL-10 旁系同源物都表现出与其哺乳动物对应物的保守功能方面。我们证明 IL-4/13A 和 IL-4/13B 是维持鳃中 Th2 样表型和抑制 1 型免疫反应所必需的。与哺乳动物一样,IL-10 似乎比 IL-4 样细胞因子具有更显着的抗炎功能,并且对于鳃内稳态至关重要。因此,斑马鱼中的 IL-4/13 和 IL-10 旁系同源物都表现出与其哺乳动物对应物的保守功能方面。我们证明 IL-4/13A 和 IL-4/13B 是维持鳃中 Th2 样表型和抑制 1 型免疫反应所必需的。与哺乳动物一样,IL-10 似乎比 IL-4 样细胞因子具有更显着的抗炎功能,并且对于鳃内稳态至关重要。因此,斑马鱼中的 IL-4/13 和 IL-10 旁系同源物都表现出与其哺乳动物对应物的保守功能方面。
更新日期:2020-07-08
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