IL-13 receptor alpha2 regulates the immune and functional response to Nippostrongylus brasiliensis infection.

IL-13 receptor alpha2 regulates the immune and functional response to Nippostrongylus brasiliensis infection.
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DOI:
10.4049/jimmunol.0804299
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发表时间:
2009-08-01
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Shea-Donohue T
Shea-Donohue T
中科院分区:
其他
文献类型:
--
作者:
Morimoto M;Zhao A;Sun R;Stiltz J;Madden KB;Mentink-Kane M;Ramalingam T;Wynn TA;Urban JF Jr;Shea-Donohue T

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IL-13在宿主防御胃肠道线虫巴西日本圆线虫中具有显著作用;然而,IL-13 R α2在肠道感染的免疫和功能应答中的作用尚不清楚。在目前的研究中,我们研究了平滑肌和上皮细胞功能的变化,以及IL-13和IL-4及其受体的基因表达的改变,使用激光捕获显微切割的特定细胞类型在小肠的N。巴西人感染的小鼠。感染诱导的IL-13 R α2基因表达上调仅限于平滑肌,并依赖于STAT 6和IL-13,但不依赖于IL-4。相反,IL-13 R α1的表达降低,表明IL-13α2表达的变化限制了IL-13的生物学效应。IL-13 R α2-/-小鼠中IL-13的可用性增加导致组成性上皮和平滑肌功能发生显着变化。此外,与野生型小鼠相比,IL-13 R α2−/−感染后平滑肌过度收缩和上皮细胞阻力的最大变化更早达到峰值。这与较早的Th 2免疫应答不一致,因为IL-13 R α2−/−小鼠中IL-4和IL-13的表达减弱,蠕虫排出与野生型小鼠相似。这些数据表明,IL-13 R α2通过限制感染期间IL-13的可用性,从而调节IL-13的免疫和生物学效应,在线虫感染中发挥重要作用。
IL-13 has a prominent role in host defense against the gastrointestinal nematode Nippostrongylus brasiliensis; however, the role of IL-13Rα2 in the immune and functional response to enteric infection is not known. In the current study, we investigated changes in smooth muscle and epithelial cell function as well as alterations in gene expression of IL-13 and IL-4 and their receptors using laser-capture microdissection of specific cell types in the small intestine of N. brasiliensis-infected mice. An infection-induced up-regulation of IL-13Rα2 gene expression was confined to smooth muscle and was dependent on STAT6 and IL-13, but not on IL-4. In contrast, expression of IL-13Rα1 was reduced, indicating that changes in IL-13α2 expression serve to limit the biological effects of IL-13. The increased availability of IL-13 in IL-13Rα2−/− mice resulted in marked changes in constitutive epithelial and smooth muscle function. In addition, maximal changes in smooth muscle hypercontractility and epithelial cell resistance peaked earlier after infection in IL-13Rα2−/− compared with wild-type mice. This did not coincide with an earlier Th2 immune response as expression of IL-4 and IL-13 was attenuated in IL-13Rα2−/− mice and worm expulsion was similar to that of wild-type mice. These data show that IL-13Rα2 plays an important role in nematode infection by limiting the availability of IL-13 during infection, thereby regulating both the immune and biological effects of IL-13.
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影响因子: 4.4
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