Microbiome-driven allergic lung inflammation is ameliorated by short-chain fatty acids
Microbiome-driven allergic lung inflammation is ameliorated by short-chain fatty acids
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DOI：
10.1038/mi.2017.75
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发表时间：
2018-05-01
影响因子：
8
通讯作者：
Mohn, W. W.
中科院分区：
文献类型：
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作者：
Cait, A.;Hughes, M. R.;Mohn, W. W.
哺乳动物的胃肠道中存在着对宿主健康至关重要的代谢活性的微生物群落，包括可以调节免疫细胞效应功能的代谢物。用万古霉素治疗的小鼠具有改变的微生物组和代谢物谱，表现出加剧的辅助性T细胞2型（Th 2）应答，并且更容易发生过敏性肺部炎症。在这里，我们表明，膳食补充短链脂肪酸（SCFAs）通过调节T细胞和树突状细胞（DC）的活性来改善这种增强的哮喘易感性。用SCFA治疗的生态失调小鼠产生白细胞介素-4（IL 4）的CD 4（+）T细胞减少，循环免疫球蛋白E（IgE）水平降低。此外，暴露于SCFA的DC激活T细胞的强度较低，在体外对CCL 19的反应较低，并且表现出将吸入的过敏原转运至肺引流结的能力减弱。因此，我们的数据表明，肠道生态失调可以通过SCFA抑制的T细胞和DC依赖性机制加剧过敏性肺部炎症。
The mammalian gastrointestinal tract harbors a microbial community with metabolic activity critical for host health, including metabolites that can modulate effector functions of immune cells. Mice treated with vancomycin have an altered microbiome and metabolite profile, exhibit exacerbated T helper type 2 cell (Th2) responses, and are more susceptible to allergic lung inflammation. Here we show that dietary supplementation with short-chain fatty acids (SCFAs) ameliorates this enhanced asthma susceptibility by modulating the activity of T cells and dendritic cells (DCs). Dysbiotic mice treated with SCFAs have fewer interleukin-4 (IL4)-producing CD4(+) T cells and decreased levels of circulating immunoglobulin E (IgE). In addition, DCs exposed to SCFAs activate T cells less robustly, are less motile in response to CCL 19 in vitro, and exhibit a dampenedability to transport inhaled allergens to lung draining nodes. Our data thus demonstrate that gut dysbiosis can exacerbate allergic lung inflammation through both Tcell-and DC-dependent mechanisms that are inhibited by SCFAs.