Science：肺炎起源于肠道

这是Science杂志发表的一项重要的肠道免疫细胞迁移到肺部参与肺部免疫反应的研究，首次提示炎症性2型天然淋巴细胞会从肠道转移到肺部，参与肺部炎症。研究论文和同期对此的介绍都很值得专业人士认真看看。

Lung inflammation originating in the gut

Science  

DOI: 10.1126/science.aar4301

论文摘要

Innate lymphoid cells (ILCs) are a type of immune cell that are considered to be tis- sue-resident gatekeepers situated in mu- cosal membranes, where they contribute to both homeostasis and pathology (1). In healthy individuals, ILCs are involved in tissue repair, but ILCs have also been shown to participate in several types of inflamma- tion, including allergy and asthma. Whereas ILCs can be found at low frequencies in the blood circulation, mucosal barriers such as the intestine and airways are enriched for ILCs (1). However, whether ILCs are in fact tissue resident in the sense that they self- renew without substantial replenishment from other organs has been a topic of de- bate. The mechanisms of ILC circulation are important for understanding various types of inflammatory conditions and how they can be treated. On page 114 of this is- sue, Huang et al. (2) demonstrate that ILC2s are not obligate tissue-resident cells because they can be recruited from the gut to the lung and other organs in response to inflam- matory signaling. 

ILC2s contribute to so-called “type 2 im- munity” in which they are typically acti- vated by the cytokines interleukin-25 (IL-25) and IL-33 to produce large amounts of IL-5 and IL-13, which are key players in this type of inflammation. In 2015, Huang et al. (3) described a population of lung ILC2s char- acterized by high expression of killer cell lectin-like receptor subfamily G member 1 (KLRG1) and the IL-25 receptor, IL-17 recep- tor-b (IL-17Rb), but low expression of the IL-33 receptor, ST2 (KLRG1high ST2low ILC2s). In contrast to natural ILC2s (nILC2s), which reside in the lungs during homeostatic con- ditions, KLRG1high ST2low ILC2s were termed inflammatory ILC2s (iILC2s) as they arise in the lungs only after type 2 immunity induced by IL-25 exposure or gastrointesti- nal infection with the parasitic worm Nip- postrongylus brasiliensis. Now Huang et al. (2) extend their observations using a model to study circulation of blood-borne cells be- tween two surgically connected (parabiotic) mice to show that iILC2s accumulate in the lungs during these conditions because they are rapidly recruited within 3 to 5 days. These data challenge the existing view es- tablished following the seminal paper by Gasteiger et al. (4), who did not observe replenishment of ILC2s until day 15 after N. brasiliensis infection in parabiotic mice. The discrepancy in timing of ILC2 recruit- ment between these two studies might be due to different conditions in which mice were housed. Gasteiger et al. kept their mice on antibiotic treatment, whereas Huang et al. (2) did not. It is therefore possible that the intestinal microbiota might play an im- portant role in ILC2 circulation. 

实验综述

① 天然淋巴细胞（ILC），参与机体的稳态和哮喘等病理过程；

② Huang等证实，IL-25诱导ILC2从肠道迁移至肺部，即通过ILC2的肠-肺募集轴参与“2型免疫”；

③ 炎症性（iILC2）通过淋巴系统循环入血，可通过淋巴-上皮屏障；

④ iILC2和nILC2在肺内发挥不同的作用，iILC2由肠道募集于肺参与快速和一过性2型免疫，而nILC2主要常驻于组织，对病毒感染进行应答；

⑤ 1-磷酸鞘氨醇（S1P）受体S1P1抑制剂ozanimod可用于慢性炎症性肺疾病，如哮喘、COPD等。