Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Science. 2012 Jun 8;336(6086):1321-5. doi: 10.1126/science.1222551. Epub 2012 Jun 6.
The mammalian intestinal tract is colonized by trillions of beneficial commensal bacteria that are anatomically restricted to specific niches. However, the mechanisms that regulate anatomical containment remain unclear. Here, we show that interleukin-22 (IL-22)-producing innate lymphoid cells (ILCs) are present in intestinal tissues of healthy mammals. Depletion of ILCs resulted in peripheral dissemination of commensal bacteria and systemic inflammation, which was prevented by administration of IL-22. Disseminating bacteria were identified as Alcaligenes species originating from host lymphoid tissues. Alcaligenes was sufficient to promote systemic inflammation after ILC depletion in mice, and Alcaligenes-specific systemic immune responses were associated with Crohn's disease and progressive hepatitis C virus infection in patients. Collectively, these data indicate that ILCs regulate selective containment of lymphoid-resident bacteria to prevent systemic inflammation associated with chronic diseases.
哺乳动物的肠道中定植着数以万亿计的有益共生菌，这些共生菌在解剖学上局限于特定的生态位。然而，调节解剖学限制的机制尚不清楚。在这里，我们表明，白细胞介素 22（IL-22）产生的固有淋巴细胞（ILC）存在于健康哺乳动物的肠道组织中。ILC 的耗竭导致共生菌的外周播散和全身炎症，而 IL-22 的给药可预防这种情况。播散的细菌被鉴定为源自宿主淋巴组织的产碱杆菌属物种。在小鼠中耗尽 ILC 后，产碱杆菌足以促进全身炎症，并且与克罗恩病和丙型肝炎病毒感染的进展相关的是针对产碱杆菌的全身性免疫反应。总的来说，这些数据表明 ILC 调节淋巴组织驻留细菌的选择性限制，以防止与慢性疾病相关的全身炎症。
