Enterocytes, fibroblasts and myeloid cells synergize in anti-bacterial and anti-viral pathways with IL22 as the central cytokine.
Enterocytes, fibroblasts and myeloid cells synergize in anti-bacterial and anti-viral pathways with IL22 as the central cytokine.
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DOI：
10.1038/s42003-021-02176-0
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发表时间：
2021-05-27
影响因子：
5.9
通讯作者：
Pieters R
中科院分区：
文献类型：
--
作者：
Klooster JPT;Bol-Schoenmakers M;van Summeren K;van Vliet ALW;de Haan CAM;van Kuppeveld FJM;Verkoeijen S;Pieters R
il - 22是参与肠道微生物防御机制的重要细胞因子。通过回肠类器官，我们发现il - 22可以诱导抗微生物肽（AMPs）和抗病毒肽（AVPs）的表达。此外，我们确定了细菌和病毒途径，两者都导致T细胞产生il - 22，但通过不同的途径。细菌产物，如LPS，诱导肠细胞分泌SAA1，触发成纤维细胞分泌il - 6，随后触发T细胞分泌il - 22。巨噬细胞来源的TNFα可以通过两种方式增强这种il - 22诱导：通过增强T细胞对il - 6的反应性和通过增加成纤维细胞对il - 6的表达。病毒感染肠细胞诱导IFNβ1和随后的IL7。IFNβ1可诱导成纤维细胞中IL6的表达，IL6和IL7的联合活性可诱导T细胞中IL22的表达。我们还发现，IL22降低了病毒进入受体（如ACE2、TMPRSS2、DPP4、CD46和TNFRSF14）的表达，增加了抗病毒蛋白（如RSAD2、AOS、ISG20和Mx1）的表达，从而降低了邻近细胞的病毒感染。总的来说，我们的数据表明，IL22有助于对抗细菌和病毒的先天反应。10 Klooster等人利用回肠衍生的类器官报道，细菌和病毒刺激可以通过不同的信号通路驱动T细胞产生IL22，并且IL22可以刺激抗微生物和抗病毒因子的表达。这项研究揭示了肠细胞、成纤维细胞和髓细胞如何协同作用，诱导il - 22对细菌和病毒的反应。
IL22 is an important cytokine involved in the intestinal defense mechanisms against microbiome. By using ileum-derived organoids, we show that the expression of anti-microbial peptides (AMPs) and anti-viral peptides (AVPs) can be induced by IL22. In addition, we identified a bacterial and a viral route, both leading to IL22 production by T cells, but via different pathways. Bacterial products, such as LPS, induce enterocyte-secreted SAA1, which triggers the secretion of IL6 in fibroblasts, and subsequently IL22 in T cells. This IL22 induction can then be enhanced by macrophage-derived TNFα in two ways: by enhancing the responsiveness of T cells to IL6 and by increasing the expression of IL6 by fibroblasts. Viral infections of intestinal cells induce IFNβ1 and subsequently IL7. IFNβ1 can induce the expression of IL6 in fibroblasts and the combined activity of IL6 and IL7 can then induce IL22 expression in T cells. We also show that IL22 reduces the expression of viral entry receptors (e.g. ACE2, TMPRSS2, DPP4, CD46 and TNFRSF14), increases the expression of anti-viral proteins (e.g. RSAD2, AOS, ISG20 and Mx1) and, consequently, reduces the viral infection of neighboring cells. Overall, our data indicates that IL22 contributes to the innate responses against both bacteria and viruses. ten Klooster et al. use ileum-derived organoids and report that bacterial and viral stimuli can drive IL22 production by T cells via distinct signaling pathways, and that IL22 can stimulate expression of anti-microbial and antiviral factors. This study sheds light on how enterocytes, fibroblasts and myeloid cells work synergistically to induce IL22 response against both bacteria and viruses.
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影响因子：
64.8
作者：
Li W;Moore MJ;Vasilieva N;Sui J;Wong SK;Berne MA;Somasundaran M;Sullivan JL;Luzuriaga K;Greenough TC;Choe H;Farzan M
通讯作者：
Farzan M
影响因子：
4.9
作者：
Lopes, Susana;Andrade, Patricia;Macedo, Guilherme
通讯作者：
Macedo, Guilherme
影响因子：
56.9
作者：
Lamers, Mart M.;Beumer, Joep;Clevers, Hans
通讯作者：
Clevers, Hans
影响因子：
30.5
作者：
Duhen, Thomas;Geiger, Rebekka;Sallusto, Federica
通讯作者：
Sallusto, Federica
影响因子：
5.4
作者：
Burkard, Christine;Verheije, Monique H.;de Haan, Cornelis A. M.
通讯作者：
de Haan, Cornelis A. M.