Orally desensitized mast cells form a regulatory network with Treg cells for the control of food allergy.
Orally desensitized mast cells form a regulatory network with Treg cells for the control of food allergy.
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DOI：
10.1038/s41385-020-00358-3
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发表时间：
2021-05
影响因子：
8
通讯作者：
Kiyono H
中科院分区：
文献类型：
--
作者：
Takasato Y;Kurashima Y;Kiuchi M;Hirahara K;Murasaki S;Arai F;Izawa K;Kaitani A;Shimada K;Saito Y;Toyoshima S;Nakamura M;Fujisawa K;Okayama Y;Kunisawa J;Kubo M;Takemura N;Uematsu S;Akira S;Kitaura J;Takahashi T;Nakayama T;Kiyono H
口服免疫疗法(OIT)是控制食物过敏的有效方法。虽然目前还不清楚OIT的详细分子和细胞机制，但必须了解它们才能促进过敏性疾病的治疗。为了阐明OIT的发病机制，特别是在从免疫脱敏到免疫调节的过程中，我们建立了一种临床OIT小鼠模型，并用它来检测OIT的免疫学事件。我们发现，在成功完成OIT的小鼠中，脱敏的肥大细胞(MC)显示出功能上的有益变化，例如调节性细胞因子的诱导增加和调节性T细胞的增强扩张。重要的是，在缺乏OIT诱导的脱敏MC的小鼠中，这些调节T细胞介导的过敏反应抑制作用显著降低。总而言之，这些发现表明，脱敏过程调节MC的激活，直接导致调节性T细胞扩张的增强诱导，并促进临床过敏无反应。我们的结果表明，有效地诱导调节性MC是治疗变态反应性疾病的一种新策略。
Oral immunotherapy (OIT) is an effective approach to controlling food allergy. Although the detailed molecular and cellular mechanisms of OIT are unknown currently, they must be understood to advance the treatment of allergic diseases in general. To elucidate the mechanisms of OIT, especially during the immunological transition from desensitization to allergy regulation, we generated a clinical OIT murine model and used it to examine immunological events of OIT. We found that in mice that completed OIT successfully, desensitized mast cells (MCs) showed functionally beneficial alterations, such as increased induction of regulatory cytokines and enhanced expansion of regulatory T cells. Importantly, these regulatory-T-cell-mediated inhibitions of allergic responses were dramatically decreased in mice lacking OIT-induced desensitized MC. Collectively, these findings show that the desensitization process modulates the activation of MCs, leading directly to enhanced induction of regulatory-T-cell expansion and promotion of clinical allergic unresponsiveness. Our results suggest that efficiently inducing regulatory MCs is a novel strategy for the treatment of allergic disease.
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DOI：
10.1172/jci87492
发表时间：
2016-11-01
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
Ang WX;Church AM;Kulis M;Choi HW;Burks AW;Abraham SN
通讯作者：
Abraham SN
影响因子：
4.4
作者：
Bonnet, Benjamin;Vigneron, James;Bellier, Bertrand
通讯作者：
Bellier, Bertrand
影响因子：
14.2
作者：
Khodoun, Marat V.;Kucuk, Zeynep Yesim;Finkelman, Fred D.
通讯作者：
Finkelman, Fred D.
影响因子：
14.2
作者：
Dawicki, Wojciech;Li, Chunyan;Gordon, John R.
通讯作者：
Gordon, John R.
DOI：
10.1056/nejmoa1200435
发表时间：
2012-07-19
期刊：
The New England journal of medicine
影响因子：
--
作者：
Burks AW;Jones SM;Wood RA;Fleischer DM;Sicherer SH;Lindblad RW;Stablein D;Henning AK;Vickery BP;Liu AH;Scurlock AM;Shreffler WG;Plaut M;Sampson HA;Consortium of Food Allergy Research (CoFAR)
通讯作者：
Consortium of Food Allergy Research (CoFAR)