Mizuno Natsumi, Sasaki Yusuke, Segawa Ryosuke, Asakawa Sanki, Hiratsuka Masahiro, Hirasawa Noriyasu
Laboratory of Pharmacotherapy of Life-Style Related Diseases, Graduate School of Pharmaceutical Sciences, Tohoku University, Japan.
Laboratory of Pharmacotherapy of Life-Style Related Diseases, Graduate School of Pharmaceutical Sciences, Tohoku University, Japan.
Immunobiology. 2018 Jan;223(1):25-31. doi: 10.1016/j.imbio.2017.10.018. Epub 2017 Oct 9.
Immunological mechanisms of hygiene hypothesis are expected to develop a novel strategy for allergy prevention. Although a large number of studies has investigated the relation between allergies and infection, little is known about the influence of the exposure to infections on antigen uptake by dendritic cells (DCs). In this study, we examined the effect of lipopolysaccharide (LPS) priming in early life on the antigen uptake ability of DCs by using an original mouse model. LPS priming in juvenile mice decreased the migration of antigen-capturing CD11c cells in the lymph nodes, but not in aged mice. Besides, the bone marrow-derived DCs (BMDCs) from juvenile LPS-primed mice had the poor antigen uptake ability, and constitutively produced NO through the inducible nitric oxide synthase (iNOS). Interestingly, the LPS priming-induced poor antigen uptake of BMDCs was mimicked by the NO donor, and recovered by the iNOS inhibitor. Additionally, LPS priming in juvenile mice prevented the allergic reactions, but not in aged mice. Our results suggested that an exposure to infections in early life prevents allergy through the alteration of the BM cells fate that is to induce the differentiation of BM cells into inhibitory DCs such as NO-producing DCs.
卫生假说的免疫机制有望开发出一种预防过敏的新策略。尽管大量研究探讨了过敏与感染之间的关系，但对于感染暴露对树突状细胞（DCs）摄取抗原的影响却知之甚少。在本研究中，我们通过使用一种原始小鼠模型，研究了生命早期脂多糖（LPS）预处理对DCs抗原摄取能力的影响。幼年小鼠的LPS预处理减少了淋巴结中捕获抗原的CD11c细胞的迁移，但老年小鼠中未出现这种情况。此外，来自幼年LPS预处理小鼠的骨髓来源DCs（BMDCs）具有较差的抗原摄取能力，并通过诱导型一氧化氮合酶（iNOS）持续产生一氧化氮（NO）。有趣的是，NO供体模拟了LPS预处理诱导的BMDCs抗原摄取能力下降，而iNOS抑制剂可使其恢复。此外，幼年小鼠的LPS预处理可预防过敏反应，但老年小鼠中则不然。我们的结果表明，生命早期暴露于感染可通过改变骨髓细胞命运来预防过敏，即诱导骨髓细胞分化为抑制性DCs，如产生NO的DCs。
