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Co-adjuvant effects of retinoic acid and IL-15 induce inflammatory immunity to dietary antigens

机译：视黄酸和IL-15的共佐剂作用诱导对饮食抗原的炎症免疫

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摘要

Under physiological conditions the gut-associated lymphoid tissues not only prevent the induction of a local inflammatory immune response, but also induce systemic tolerance to fed antigens1>2. A notable exception is coeliac disease, where genetically susceptible individuals expressing human leukocyte antigen (HLA) HLA-DQ2 or HLA-DQ8 molecules develop inflammatory T-cell and antibody responses against dietary gluten, a protein present in wheat3. The mechanisms underlying this dysregulated mucosal immune response to a soluble antigen have not been identified. Retinoic acid, a metabolite of vitamin A, has been shown to have a critical role in the induction of intestinal regulatory responses4"6. Here we find in mice that in conjunction with IL-15, a cytokine greatly upregulated in the gut of coeliac disease patients3'7, retinoic acid rapidly activates dendritic cells to induce JNK (also known as MAPK8) phosphoryla-tion and release the proinflammatory cytokines IL-12p70 and IL-23. As a result, in a stressed intestinal environment, retinoic acid acted as an adjuvant that promoted rather than prevented inflammatory cellular and humoral responses to fed antigen. Altogether, these findings reveal an unexpected role for retinoic acid and IL-15 in the abrogation of tolerance to dietary antigens.%维他命A代谢物视黄酸，被发现与细胞因子“白rn介素-15”(IL-15)协同作用，诱导小肠树状细rn胞产生IL-12p70，从而促进炎性T-细胞对食物rn性抗原的反应。IL-15在腹腔疾病患者肠道中数rn量增加，这项新的研究工作指出了IL-15和视黄rn酸在促进针对谷蛋白的炎性免疫反应中所起的rn一种以前不知道的作用。
机译：在生理条件下，肠道相关的淋巴组织不仅阻止了局部炎症免疫反应的诱导，而且还诱导了对进食抗原的系统耐受1> 2。腹腔疾病是一个显着的例外，在这种疾病中，表达人类白细胞抗原（HLA）HLA-DQ2或HLA-DQ8分子的遗传易感个体产生了针对饮食麸质（小麦中存在的蛋白质）的炎性T细胞和抗体应答。尚不清楚这种针对可溶性抗原的粘膜免疫反应失调的机制。维甲酸是维生素A的代谢产物，已被证明在诱导肠道调节反应中起着关键作用4“ 6。在小鼠中，我们发现与IL-15结合的乳糜泻肠道中的细胞因子大大上调。在3'7号患者中，视黄酸会迅速激活树突状细胞，从而诱导JNK（也称为MAPK8）磷酸化并释放促炎细胞因子IL-12p70和IL-23，因此在紧张的肠道环境中，视黄酸充当了总的来说，这些发现揭示了视黄酸和IL-15在消除对饮食抗原的耐受性中具有意想不到的作用。与细胞因子“白rn介素-15”（IL-15）协同作用，诱导小肠树状细rn胞产生IL-12p70，从而促进炎性T-细胞对食物rn性抗原的反应。IL-15在腹腔疾病患者体内中数量增加，这新的研究工作指出了IL-15和视黄rn酸在促进针对谷蛋白的炎性免疫反应中所起的rn一种以前不知道的作用。

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  • 来源
    《Nature》 |2011年第7337期|p.220-224|共5页
  • 作者

    R. W. DePaolo; V. Abadie; F. Tang; H. Fehlner-Peach; J. A. Hall; W. Wang; E. V. Marietta; D. D. Kasarda; T. A. Waldmann; J. A. Murray; C. Semrad; S. S. Kupfer; Y. Belkaid; S. Guandalini; B. Jabri;

  • 作者单位

    Department of Medicine, University of Chicago, Chicago, Illinois 60637, USA;

    Department of Medicine, University of Chicago, Chicago, Illinois 60637, USA;

    Department of Medicine, University of Chicago, Chicago, Illinois 60637, USA;

    Department of Medicine, University of Chicago, Chicago, Illinois 60637, USA;

    Mucosal Immunology Unit, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA,Immunology Graduate Group, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA;

    Department of Medicine, University of Chicago, Chicago, Illinois 60637, USA;

    Department of Dermatology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA,Department of Immunology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA;

    US Department of Agriculture, Agricultural Research Service, Western Regional Research Center, 800 Buchanan Street, Albany, California 94710, USA;

    Metabolism Branch, National Cancer Institute, Bethesda, Maryland 20892-1374, USA;

    Department of Medicine, Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA;

    Department of Medicine, University of Chicago, Chicago, Illinois 60637, USA;

    Department of Medicine, University of Chicago, Chicago, Illinois 60637, USA;

    Mucosal Immunology Unit, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA;

    Department of Pediatrics, University of Chicago, Chicago, Illinois 60637, USA;

    Department of Medicine, University of Chicago, Chicago, Illinois 60637, USA,Department of Pediatrics, University of Chicago, Chicago, Illinois 60637, USA,Department of Medicine, University of Chicago, Chicago, Illinois 60637, 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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