Oral tolerance inhibits atopic dermatitis-like type 2 inflammation in mice by modulating immune microenvironments
Oral tolerance inhibits atopic dermatitis-like type 2 inflammation in mice by modulating immune microenvironments
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DOI：
10.1111/all.12960
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发表时间：
2017-03-01
期刊：
影响因子：
12.4
通讯作者：
Jung, Y.
中科院分区：
文献类型：
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作者：
Baek, J. O.;Roh, J. Y.;Jung, Y.
背景：口服免疫耐受是指口服无害抗原诱导的免疫无反应性。已显示口服施用过敏原可有效抑制过敏反应中的IgE产生。然而，口服耐受性是否具有保护过敏性皮肤炎症的作用尚未得到充分研究。在这里，我们评估了潜在的保护作用，口服耐受性在小鼠模型的特应性皮炎（AD）和调查的免疫mechanism.Methods：小鼠喂以卵清蛋白（OVA）在饮用水，然后epicuperatum致敏反复应用的OVA磁带剥离皮肤。分析皮肤活检的免疫组织病理学特征。通过ELISA测量血清和肠洗液中的抗体水平。流式细胞术和实时荧光PCR分析的皮肤和肠系膜淋巴结（MLN）进行调查的免疫学效应的口服耐受在表皮（EC）致敏诱导的过敏responses.Results：诱导口服耐受有效地抑制炎症反应引起的EC致敏。致耐受性免疫介质显着增加EC致敏小鼠的皮肤和MLN口服耐受诱导后。IL 5和IL 13的表达和嗜酸性粒细胞和2型先天性淋巴细胞（ILC2）在EC致敏小鼠皮肤中的浸润显着增加，显着抑制口服tolerance.Conclusions：口服耐受在AD小鼠模型的发展中起着保护作用，通过调节免疫微环境，更有利于免疫调节。这种调节涉及皮肤病变中ILC2浸润的抑制。
Background: Oral tolerance is immune unresponsiveness induced by oral administration of innocuous antigens. Oral administration of allergens has been shown to be effective for suppressing IgE production in allergic responses. However, whether oral tolerance has a role in protection from allergic skin inflammation has not been fully investigated. Here, we evaluated the potential protective role of oral tolerance in a murine model of atopic dermatitis (AD) and investigated the underlying immunologic mechanisms.Methods: Mice were fed with ovalbumin (OVA) in drinking water then epicutaneously sensitized by repeated application of OVA to tape-stripped skin. Skin biopsies were analyzed for immunohistopathologic features. Levels of antibodies in sera and intestinal washes were measured by ELISA. Flow cytometry and real-time PCR analysis of the skin and mesenteric lymph nodes (MLN) were performed to investigate the immunologic effects of oral tolerance in epicutaneous (EC) sensitization-induced allergic responses.Results: Induction of oral tolerance effectively inhibited inflammatory responses provoked by EC sensitization. Tolerogenic immune mediators were significantly increased in the skin and MLN of EC-sensitized mice following induction of oral tolerance. A marked increase in Il5 and Il13 expression and infiltration of eosinophils and type 2 innate lymphoid cells (ILC2) in the skin of EC-sensitized mice were significantly inhibited by oral tolerance.Conclusions: Oral tolerance plays a protective role in the development of AD in a murine model by modulating immune microenvironments to be more favorable for immune regulation. This modulation involves inhibition of ILC2 infiltration in skin lesions.