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Type 2 innate lymphoid cells control eosinophil homeostasis

机译:2型先天淋巴样细胞控制嗜酸性粒细胞的体内稳态

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摘要

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 eosino-philopoiesis and tissue eosinophil accumulation through constitutive and stimulated cytokine expression, and this dissociated regulation can be tuned by nutrient intake and central circadian rhythms.
机译:嗜酸性粒细胞是与变态反应和蠕虫感染相关的特化髓样细胞。血液嗜酸性粒细胞表现出昼夜节律性循环,如80年前所述,并且在健康的胃肠道中含量丰富。尽管细胞因子,白介素(IL)-5和趋化因子(例如eotaxins)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的基础过程仍然未知。在这里我们显示,血清IL-5水平由居住在外周组织中的长寿2型先天淋巴样细胞(ILC2)维持。 ILC2细胞组成性分泌IL-5,并在2型炎症过程中被诱导共表达IL-13,导致局部嗜酸性粒细胞生成和嗜酸性粒细胞积累。在嗜酸性粒细胞和嗜酸性粒细胞趋化因子组成的小肠中,ILC2细胞共表达IL-5和IL-13。摄入热量后,这种共表达增强。昼夜节律同步器血管活性肠肽还通过VPAC2受体刺激ILC2细胞释放IL-5,使嗜酸性粒细胞水平与代谢循环相关。组织ILC2细胞通过组成型和刺激性细胞因子表达来调节基础嗜酸性粒细胞和组织嗜酸性粒细胞的积累,而这种解离的调节可以通过营养摄入和中央昼夜节律来调节。

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  • 来源
    《Nature》 |2013年第7470期|245-248|共4页
  • 作者单位

    Department of Medicine, University of California San Francisco, San Francisco, California 94143-0795, USA;

    Department of Medicine, University of California San Francisco, San Francisco, California 94143-0795, USA;

    Department of Medicine, University of California San Francisco, San Francisco, California 94143-0795, USA;

    Department of Pediatrics, University of California San Francisco, San Francisco, California 94143-0795, USA;

    Departments of Microbiology & Immunology, University of California San Francisco, San Francisco, California 94143-0795, USA;

    Department of Laboratory Medicine, University of California San Francisco, San Francisco, California 94143-0795, USA;

    Department of Pathology, University of California San Francisco, San Francisco, California 94143-0795, USA;

    Department of Pathology, University of California San Francisco, San Francisco, California 94143-0795, USA;

    Department of Medicine, University of California San Francisco, San Francisco, California 94143-0795, USA,Department of Physiology, University of California San Francisco, San Francisco, California 94143-0795, USA,Cardiovascular Research Institute, University of California San Francisco, San Francisco, California 94143-0795, USA;

    Department of Medicine, University of California San Francisco, San Francisco, California 94143-0795, USA;

    Department of Medicine, University of California San Francisco, San Francisco, California 94143-0795, USA,Departments of Microbiology & Immunology, University of California San Francisco, San Francisco, California 94143-0795, USA,Howard Hughes Medical Institute, University of California San Francisco, San Francisco, California 94143-0795, USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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