Engineering Lab of Henan Province for Aquatic Animal Disease Control, College of Fisheries, Henan Normal University, Xinxiang, Henan, 453007, China.
Engineering Lab of Henan Province for Aquatic Animal Disease Control, College of Fisheries, Henan Normal University, Xinxiang, Henan, 453007, China.
Fish Shellfish Immunol. 2022 Dec;131:796-808. doi: 10.1016/j.fsi.2022.10.051. Epub 2022 Oct 27.
Interleukin (IL)-22 is an IL-10 family cytokine secreted by CD4 T cells and plays an important role in regulating inflammation and infection elimination. IL-22 homologues have been reported in the teleost, but the functions of IL-22 are still unclear. In this study, we identified two duplicated IL-22 genes in common carp (Cyprinus carpio L.), termed Cc_IL-22A and Cc_IL-22B. Sequence analysis showed that Cc_IL-22A and Cc_IL-22B had four conserved cysteine residues, which could form two intra-chain disulfide bridges. The Cc_IL-22A and Cc_IL-22B were constitutively expressed in various tissues, with the highest expression in the gill. The mRNA expression levels of Cc_IL-22A and Cc_IL-22B were significantly up-regulated in the gill, intestine, head kidney, and spleen of common carp challenged with Aeromonas. hydrophila. In vivo study showed that the expression levels of pro-inflammatory cytokines were significantly up-regulated in the head kidney and spleen when Cc_IL-22A or Cc_IL-22B were over-expressed. Furthermore, the over-expression of Cc_IL-22A and Cc_IL-22B indicated a protective effect on tissues, with only lymphocytic infiltration observed in comparison to the control and pcN3 groups, without obvious change in tissue morphology. Similar stimulatory effects of rIL-22A and rIL-22B were observed in vitro. When HKLs were stimulated with rIL-22A or rIL-22B, the expression levels of critical signaling molecules in the Janus kinase (JAK) and signal transducer and activator of transcription (STAT) pathway were significantly induced, including JAK1, JAK3, STAT1, and STAT3, as well as pro-inflammatory cytokines (IL-1β and TNF-α). Together, these results suggest that Cc_IL-22A and Cc_IL-22B may regulate inflammatory responses through the JAK-STAT signaling pathway and have a significant impact on the immune defense of common carp against bacterial infection. Therefore, our study provides a new perspective on the functions of Cc_IL-22A and Cc_IL-22B in the immune defense mechanism of fish.
白细胞介素 (IL)-22 是一种由 CD4 T 细胞分泌的 IL-10 家族细胞因子，在调节炎症和消除感染方面发挥着重要作用。已在硬骨鱼中报道了 IL-22 的同源物，但 IL-22 的功能仍不清楚。在这项研究中，我们在鲤鱼（Cyprinus carpio L.）中鉴定了两种重复的 IL-22 基因，分别称为 Cc_IL-22A 和 Cc_IL-22B。序列分析表明，Cc_IL-22A 和 Cc_IL-22B 具有四个保守的半胱氨酸残基，可以形成两个链内二硫键。Cc_IL-22A 和 Cc_IL-22B 在各种组织中均呈组成型表达，在鳃中表达量最高。在受到嗜水气单胞菌攻击时，Cc_IL-22A 和 Cc_IL-22B 在鲤鱼的鳃、肠、头肾和脾脏中的 mRNA 表达水平显著上调。体内研究表明，当 Cc_IL-22A 或 Cc_IL-22B 过表达时，头肾和脾脏中的促炎细胞因子表达水平显著上调。此外，Cc_IL-22A 和 Cc_IL-22B 的过表达对组织具有保护作用，与对照和 pcN3 组相比，仅观察到淋巴细胞浸润，组织形态无明显变化。在体外观察到 rIL-22A 和 rIL-22B 的类似刺激作用。当 HKLs 受到 rIL-22A 或 rIL-22B 刺激时，Janus 激酶 (JAK) 和信号转导和转录激活因子 (STAT) 通路中的关键信号分子的表达水平显著诱导，包括 JAK1、JAK3、STAT1 和 STAT3 以及促炎细胞因子 (IL-1β 和 TNF-α)。综上所述，这些结果表明 Cc_IL-22A 和 Cc_IL-22B 可能通过 JAK-STAT 信号通路调节炎症反应，并对鲤鱼抵抗细菌感染的免疫防御产生重大影响。因此，我们的研究为 Cc_IL-22A 和 Cc_IL-22B 在鱼类免疫防御机制中的功能提供了新的视角。
