Department of Medicine, University of California San Francisco, San Francisco, California 94143-0795, USA.
Nature. 2013 Oct 10;502(7470):245-8. doi: 10.1038/nature12526. Epub 2013 Sep 15.
Eosinophils are specialized myeloid cells associated with allergy and helminth infections. Blood eosinophils demonstrate circadian cycling, as described over 80 years ago, and are abundant in the healthy gastrointestinal tract. Although a cytokine, interleukin (IL)-5, and chemokines such as eotaxins mediate eosinophil development and survival, and tissue recruitment, respectively, the processes underlying the basal regulation of these signals remain unknown. Here we show that serum IL-5 levels are maintained by long-lived type 2 innate lymphoid cells (ILC2) resident in peripheral tissues. ILC2 cells secrete IL-5 constitutively and are induced to co-express IL-13 during type 2 inflammation, resulting in localized eotaxin production and eosinophil accumulation. In the small intestine where eosinophils and eotaxin are constitutive, ILC2 cells co-express IL-5 and IL-13; this co-expression is enhanced after caloric intake. The circadian synchronizer vasoactive intestinal peptide also stimulates ILC2 cells through the VPAC2 receptor to release IL-5, linking eosinophil levels with metabolic cycling. Tissue ILC2 cells regulate basal eosinophilopoiesis and tissue eosinophil accumulation through constitutive and stimulated cytokine expression, and this dissociated regulation can be tuned by nutrient intake and central circadian rhythms.
嗜酸性粒细胞是与过敏和寄生虫感染相关的特化髓系细胞。正如 80 多年前所描述的那样，血液嗜酸性粒细胞表现出昼夜节律循环，并且在健康的胃肠道中丰富存在。尽管细胞因子白细胞介素（IL）-5 和趋化因子如 eotaxin 分别介导嗜酸性粒细胞的发育和存活以及组织募集，但这些信号的基础调节过程仍不清楚。在这里，我们表明，血清 IL-5 水平由驻留在外周组织中的长寿命 2 型先天淋巴细胞（ILC2）维持。ILC2 细胞持续分泌 IL-5，并在 2 型炎症期间被诱导共同表达 IL-13，导致局部 eotaxin 产生和嗜酸性粒细胞积聚。在嗜酸性粒细胞和 eotaxin 构成性存在的小肠中，ILC2 细胞共同表达 IL-5 和 IL-13；这种共表达在热量摄入后增强。昼夜同步器血管活性肠肽也通过 VPAC2 受体刺激 ILC2 细胞释放 IL-5，将嗜酸性粒细胞水平与代谢循环联系起来。组织 ILC2 细胞通过组成性和受刺激的细胞因子表达调节基础嗜酸性粒细胞生成和组织嗜酸性粒细胞积聚，这种分离的调节可以通过营养摄入和中枢昼夜节律进行调整。
