Systemic Toll-like receptor stimulation suppresses experimental allergic asthma and autoimmune diabetes in NOD mice.
Systemic Toll-like receptor stimulation suppresses experimental allergic asthma and autoimmune diabetes in NOD mice.
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DOI：
10.1371/journal.pone.0011484
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发表时间：
2010-07-07
期刊：
影响因子：
3.7
通讯作者：
Thieblemont N
中科院分区：
文献类型：
--
作者：
Aumeunier A;Grela F;Ramadan A;Pham Van L;Bardel E;Gomez Alcala A;Jeannin P;Akira S;Bach JF;Thieblemont N
感染可能与过敏性和自身免疫性疾病的恶化有关。奇怪的是，流行病学和实验数据表明，一些微生物也可以预防这些疾病。这一观察结果是卫生假说的起源，根据卫生假说，西方国家感染的下降是过去几十年来Th 1介导的自身免疫性疾病和Th 2介导的过敏性疾病发病率增加的起源。我们已经测试了Toll样受体（TLR）刺激是否可以概括感染因子对过敏和自身免疫的保护作用。在这里，我们进行了一个系统的研究，一组天然或合成的TLR激动剂的疾病修饰的影响，使用两个实验模型，卵清蛋白（OVA）诱导的哮喘和自发性自身免疫性糖尿病，提出了相同的遗传背景的非肥胖糖尿病小鼠（NOD），这是非常容易受到这两种病理。在相同的模型中，我们还研究了益生菌的作用。此外，我们研究了MyD 88基因失效对过敏性哮喘和自发性糖尿病发展的影响。我们证明了多种TLR激动剂在胃肠外给药时可预防过敏和自身免疫。刺激TLR的益生菌也可以预防这两种疾病。MyD 88失效小鼠中OVA诱导的哮喘的主要加速进一步表明了这些发现的生理相关性。我们的研究结果强烈表明TLR介导的作用涉及免疫调节细胞因子，如白细胞介素（IL）-10和TGF-β，以及调节性T细胞的不同亚群，特别是TLR 4激动剂的CD 4 + CD 25 + FoxP 3 + T细胞和TLR 3激动剂的NKT细胞。这些观察结果表明，全身施用TLR配体可以抑制过敏和自身免疫应答。它们为卫生假说提供了一个合理的解释。它们还为预防这些病理开辟了新的治疗前景。
Infections may be associated with exacerbation of allergic and autoimmune diseases. Paradoxically, epidemiological and experimental data have shown that some microorganisms can also prevent these pathologies. This observation is at the origin of the hygiene hypothesis according to which the decline of infections in western countries is at the origin of the increased incidence of both Th1-mediated autoimmune diseases and Th2-mediated allergic diseases over the last decades. We have tested whether Toll-like receptor (TLR) stimulation can recapitulate the protective effect of infectious agents on allergy and autoimmunity. Here, we performed a systematic study of the disease-modifying effects of a set of natural or synthetic TLR agonists using two experimental models, ovalbumin (OVA)-induced asthma and spontaneous autoimmune diabetes, presenting the same genetic background of the non obese diabetic mouse (NOD) that is highly susceptible to both pathologies. In the same models, we also investigated the effect of probiotics. Additionally, we examined the effect of the genetic invalidation of MyD88 on the development of allergic asthma and spontaneous diabetes. We demonstrate that multiple TLR agonists prevent from both allergy and autoimmunity when administered parenterally. Probiotics which stimulate TLRs also protect from these two diseases. The physiological relevance of these findings is further suggested by the major acceleration of OVA-induced asthma in MyD88 invalidated mice. Our results strongly indicate that the TLR-mediated effects involve immunoregulatory cytokines such as interleukin (IL)-10 and transforming growth factor (TGF)-β and different subsets of regulatory T cells, notably CD4+CD25+FoxP3+ T cells for TLR4 agonists and NKT cells for TLR3 agonists. These observations demonstrate that systemic administration of TLR ligands can suppress both allergic and autoimmune responses. They provide a plausible explanation for the hygiene hypothesis. They also open new therapeutic perspectives for the prevention of these pathologies.
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影响因子：
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