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虹鳟鱼的免疫刺激揭示了 MH 类 II 相关不变链同工型的不同调节。

Immune stimulation of rainbow trout reveals divergent regulation of MH class II-associated invariant chain isoforms.

机构信息

Department of Biology, University of Waterloo, 200 University Ave W., Waterloo, ON, N2L 3G1, Canada.

出版信息

Immunogenetics. 2019 May;71(5-6):407-420. doi: 10.1007/s00251-019-01115-y. Epub 2019 Apr 29.

Abstract

Major histocompatibility complex (MHC) class II-associated invariant chain is a chaperone responsible for targeting the MHC class II dimer to the endocytic pathway, thus enabling the loading of exogenous antigens onto the MHC class II receptor. In the current study, in vivo and in vitro methods were used to investigate the regulation of the rainbow trout invariant chain proteins S25-7 and INVX, upon immune system activation. Whole rainbow trout and the macrophage/monocyte-like cell line RTS11 were treated with PMA at concentrations shown to induce IL-1β transcripts and homotypic aggregation of RTS11. S25-7 transcript levels remained unchanged in the gill, spleen, and liver and were found to be significantly decreased in head kidney beginning 24 h post-stimulation. Meanwhile, INVX transcript levels remained unchanged in all tissues studied. Both S25-7 and INVX proteins were produced in gill and spleen tissues but their expression was unaffected by immune system stimulation. Surprisingly, neither INVX nor S25-7 protein was detected in the secondary immune organ, the head kidney. Analysis of RTS11 cultures demonstrated that both INVX and S25-7 transcript levels significantly increased at 96 h and 120 h following PMA stimulation before returning to control levels at 168 h. Meanwhile, at the protein level in RTS11, S25-7 remained unchanged while INVX had a significant decrease at 168 h post-stimulation. These results indicate that neither INVX nor S25-7 is upregulated upon immune system activation; thus, teleosts have evolved a system of immune regulation that is different than that found in mammals.

摘要

主要组织相容性复合体(MHC)Ⅱ类相关不变链是一种伴侣蛋白,负责将 MHC Ⅱ类二聚体靶向内吞途径,从而使外源性抗原加载到 MHC Ⅱ类受体上。在本研究中,使用体内和体外方法研究了 Rainbow trout 不变链蛋白 S25-7 和 INVX 在免疫系统激活时的调节。用 PMA 处理 Rainbow trout 全长和巨噬细胞/单核细胞样细胞系 RTS11,浓度显示可诱导 IL-1β 转录物和 RTS11 的同型聚集。在刺激后 24 h,S25-7 转录物水平在鳃、脾和肝中保持不变,并且在头肾中发现显著降低。同时,在所有研究的组织中 INVX 转录物水平保持不变。S25-7 和 INVX 蛋白均在鳃和脾组织中产生,但它们的表达不受免疫系统刺激的影响。令人惊讶的是,在次级免疫器官头肾中未检测到 INVX 或 S25-7 蛋白。对 RTS11 培养物的分析表明,在 PMA 刺激后 96 h 和 120 h,INVX 和 S25-7 的转录物水平显著增加,然后在 168 h 恢复到对照水平。同时,在 RTS11 的蛋白质水平上,S25-7 保持不变,而 INVX 在刺激后 168 h 显著下降。这些结果表明,在免疫系统激活时,INVX 和 S25-7 均未上调;因此,硬骨鱼已经进化出一种不同于哺乳动物的免疫调节系统。

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