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白细胞介素-13/白细胞介素-4受体途径对于巴西日圆线虫感染小鼠小肠黏膜中Sd-唾液酸黏蛋白的产生至关重要。

Interleukin-13/interleukin-4 receptor pathway is crucial for production of Sd-sialomucin in mouse small intestinal mucosa by Nippostrongylus brasiliensis infection.

作者信息

Tsubokawa Daigo, Ishiwata Kenji, Goso Yukinobu, Nakamura Takeshi, Hatta Takeshi, Ishihara Kazuhiko, Kanuka Hirotaka, Tsuji Naotoshi

机构信息

Department of Parasitology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami, Sagamihara, Kanagawa 252-0374, Japan.

Department of Tropical Medicine, The Jikei University School of Medicine, 3-25-8, Nishi-shinbashi, Minato-ku, Tokyo 105-8461, Japan.

出版信息

Parasitol Int. 2017 Dec;66(6):731-734. doi: 10.1016/j.parint.2017.08.004. Epub 2017 Aug 9.

Abstract

Mucin is a major component of mucus in gastrointestinal mucosa. Increase of specific sialomucins having Sd blood group antigen, NeuAcα2-3(GalNAcβ1-4)Galβ1-4GlcNAcβ-, is considered to be associated with expulsion of the parasitic intestinal nematode Nippostrongylus brasiliensis. In this study, we examined the relationship between interleukin (IL)-13 pathway and expression of Sd-sialomucins in small intestinal mucosa with N. brasiliensis infection. Nematode infection induced marked increases in small intestinal mucins that reacted with anti-Sd antibody in wild type (wt) mice. However, this increase due to infection was supressed in IL-4 receptor α deficient (IL-4Rα) mice, which lack both IL-4 and IL-13 signaling via IL-4R, and severe combined immunodeficient (SCID) mice, which have defects in B- and T-lymphocytes. Analysis using tandem mass spectroscopy showed that Sd-glycans were not expressed in small intestinal mucins in IL-4Rα and SCID mice after infection despite the appearance of Sd-glycans in the infected wt mice. Inoculation of recombinant IL-13 into the infected SCID mice restored expression of Sd-glycan. Our results suggest that the IL-13/IL-4R axis is important for the production of Sd-sialomucins in the host intestinal mucosa with parasitic nematode infection.

摘要

黏蛋白是胃肠道黏膜中黏液的主要成分。具有Sd血型抗原(NeuAcα2-3(GalNAcβ1-4)Galβ1-4GlcNAcβ-)的特定唾液黏蛋白的增加被认为与寄生性肠道线虫巴西日圆线虫的排出有关。在本研究中,我们研究了白细胞介素(IL)-13途径与巴西日圆线虫感染的小肠黏膜中Sd-唾液黏蛋白表达之间的关系。线虫感染导致野生型(wt)小鼠小肠黏蛋白中与抗Sd抗体反应的物质显著增加。然而,在缺乏通过IL-4R的IL-4和IL-13信号传导的IL-4受体α缺陷(IL-4Rα)小鼠以及B淋巴细胞和T淋巴细胞有缺陷的严重联合免疫缺陷(SCID)小鼠中,感染引起的这种增加受到抑制。串联质谱分析表明,尽管感染的wt小鼠中出现了Sd聚糖,但感染后的IL-4Rα和SCID小鼠的小肠黏蛋白中未表达Sd聚糖。将重组IL-13接种到感染的SCID小鼠中可恢复Sd聚糖的表达。我们的结果表明,IL-13/IL-4R轴对于宿主肠道黏膜在寄生线虫感染时产生Sd-唾液黏蛋白很重要。

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