Regulatory T cell reprogramming toward a Th2-cell-like lineage impairs oral tolerance and promotes food allergy.
Regulatory T cell reprogramming toward a Th2-cell-like lineage impairs oral tolerance and promotes food allergy.
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DOI：
10.1016/j.immuni.2015.02.004
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发表时间：
2015-03-17
期刊：
影响因子：
32.4
通讯作者：
Chatila, Talal A.
中科院分区：
文献类型：
--
作者：
Noval Rivas, Magali;Burton, Oliver T.;Wise, Petra;Charbonnier, Louis-Marie;Georgiev, Peter;Oettgen, Hans C.;Rachid, Rima;Chatila, Talal A.
口服免疫疗法在建立食物过敏耐受性方面的成功有限，反映出未能诱导有效的调节性T(Treg)细胞反应。我们发现，IL-4受体(IL-4R)信号增强的疾病易感小鼠(Il4raF709)表现出STAT6依赖的黏膜变应原特异性Treg细胞的生成和功能受损。这一失败与Treg细胞获得Thelper 2(Th2)细胞样表型有关，该表型也存在于食物过敏儿童的外周血变应原特异性Treg细胞中。选择性地增强Treg细胞中的IL-4R信号可诱导其重新编程为Th2样细胞和疾病易感性，而Treg细胞系特异性缺失IL4和IL13具有保护作用。IL-4R信号减弱Treg细胞抑制肥大细胞激活和扩张的能力，进而驱动Treg细胞Th2细胞重新编程。因此，中断Treg细胞Th2细胞重编程可能为食物过敏提供新的治疗策略。
Oral immunotherapy has had limited success in establishing tolerance in food allergy, reflecting failure to elicit an effective regulatory T (Treg) cell response. We show that disease-susceptible mice (Il4raF709) with enhanced IL-4 receptor (IL-4R) signaling exhibited STAT6-dependent impaired generation and function of mucosal allergen-specific Treg cells. This failure was associated with the acquisition by Treg cells of T helper 2 (Th2) cell-like phenotype, also found in peripheral blood allergen-specific Treg cells of food allergic children. Selective augmentation of IL-4R signaling in Treg cells induced their reprogramming into Th2-like cells and disease susceptibility, whereas Treg cell lineage-specific deletion of Il4 and Il13 was protective. IL-4R signaling impaired the capacity of Treg cells to suppress mast cell activation and expansion, which in turn drove Treg cell Th2 cell reprogramming. Interruption of Treg cell Th2 cell reprogramming may thus provide novel therapeutic strategies in food allergy.
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影响因子：
15.3
作者：
Apostolou, I;von Boehmer, H
通讯作者：
von Boehmer, H
影响因子：
15.3
作者：
Karlsson, MR;Rugtveit, J;Brandtzaeg, P
通讯作者：
Brandtzaeg, P
影响因子：
14.2
作者：
Berin, M. Cecilia;Mayer, Lloyd
通讯作者：
Mayer, Lloyd
影响因子：
32.4
作者：
Haribhai D;Williams JB;Jia S;Nickerson D;Schmitt EG;Edwards B;Ziegelbauer J;Yassai M;Li SH;Relland LM;Wise PM;Chen A;Zheng YQ;Simpson PM;Gorski J;Salzman NH;Hessner MJ;Chatila TA;Williams CB
通讯作者：
Williams CB
DOI：
10.1097/wox.0b013e3181defeb9
发表时间：
2010-04
期刊：
The World Allergy Organization journal
影响因子：
--
作者：
Fiocchi A;Brozek J;Schünemann H;Bahna SL;von Berg A;Beyer K;Bozzola M;Bradsher J;Compalati E;Ebisawa M;Guzman MA;Li H;Heine RG;Keith P;Lack G;Landi M;Martelli A;Rancé F;Sampson H;Stein A;Terracciano L;Vieths S
通讯作者：
Vieths S