IL-22BP dictates characteristics of Peyer's patch follicle-associated epithelium for antigen uptake.
IL-22BP dictates characteristics of Peyer's patch follicle-associated epithelium for antigen uptake.
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DOI：
10.1084/jem.20160770
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发表时间：
2017-06-05
期刊：
影响因子：
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通讯作者：
Ohno H
中科院分区：
文献类型：
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作者：
Jinnohara T;Kanaya T;Hase K;Sakakibara S;Kato T;Tachibana N;Sasaki T;Hashimoto Y;Sato T;Watarai H;Kunisawa J;Shibata N;Williams IR;Kiyono H;Ohno H
IL-22结合蛋白抑制IL-22信号传导，这对于肠内稳态是重要的。Jinnohara等人报道了IL-22结合蛋白由派尔集合淋巴结树突细胞强烈表达，并促进M细胞将细菌抗原摄取到派尔集合淋巴结中。白细胞介素-22（IL-22）根据情况对肠组织起保护和有害作用;因此，IL-22信号传导需要严格调节。IL-22结合蛋白（IL-22 BP）结合IL-22以抑制IL-22信号传导。它在肠和淋巴组织中表达，尽管其确切的分布和作用仍不清楚。在这项研究中，我们发现IL-22 BP在派伊尔集合淋巴结（PP）上皮下圆顶区的CD 11b + CD 8 α−树突状细胞中高度表达。我们发现IL-22 BP阻断了覆盖PP的卵泡相关上皮（FAE）中的IL-22信号传导，表明IL-22 BP在调节FAE的特征中起作用。正如预期的那样，IL-22 BP缺陷（Il 22 ra 2 −/−）小鼠的FAE表现出改变的特性，例如粘液和抗菌蛋白的表达增强以及显著的岩藻糖基化，这通常在FAE中受到抑制。此外，Il 22 ra 2 −/−小鼠表现出PP对细菌抗原的摄取减少，而不影响M细胞功能。因此，我们目前的研究表明，IL-22 BP通过影响FAE基因表达和功能促进细菌摄取PP。
IL-22 binding protein inhibits IL-22 signaling, which is important for intestinal homeostasis. Jinnohara et al. report that IL-22 binding protein is strongly expressed by Peyer’s patch dendritic cells and facilitates the M cell uptake of bacterial antigens into Peyer’s patches. Interleukin-22 (IL-22) acts protectively and harmfully on intestinal tissue depending on the situation; therefore, IL-22 signaling needs to be tightly regulated. IL-22 binding protein (IL-22BP) binds IL-22 to inhibit IL-22 signaling. It is expressed in intestinal and lymphoid tissues, although its precise distribution and roles have remained unclear. In this study, we show that IL-22BP is highly expressed by CD11b+CD8α− dendritic cells in the subepithelial dome region of Peyer’s patches (PPs). We found that IL-22BP blocks IL-22 signaling in the follicle-associated epithelium (FAE) covering PPs, indicating that IL-22BP plays a role in regulating the characteristics of the FAE. As expected, FAE of IL-22BP–deficient (Il22ra2−/−) mice exhibited altered properties such as the enhanced expression of mucus and antimicrobial proteins as well as prominent fucosylation, which are normally suppressed in FAE. Additionally, Il22ra2−/− mice exhibited the decreased uptake of bacterial antigens into PPs without affecting M cell function. Our present study thus demonstrates that IL-22BP promotes bacterial uptake into PPs by influencing FAE gene expression and function.