Chronic follicular bronchiolitis requires antigen-specific regulatory T cell control to prevent fatal disease progression.
Chronic follicular bronchiolitis requires antigen-specific regulatory T cell control to prevent fatal disease progression.
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DOI：
10.4049/jimmunol.1301576
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发表时间：
2013-12-01
期刊：
影响因子：
--
通讯作者：
Williams CB
中科院分区：
文献类型：
--
作者：
Schmitt EG;Haribhai D;Jeschke JC;Co DO;Ziegelbauer J;Yan K;Iwakura Y;Mishra MK;Simpson P;Salzman NH;Williams CB
为了研究调节性T（Treg）细胞对淋巴细胞充足宿主中慢性自身免疫的控制，我们创建并表征了靶向中小气道的自身免疫性肺部炎症的新模型。我们产生的转基因小鼠表达的嵌合膜蛋白组成的鸡蛋溶菌酶（mHEL）和血红蛋白（Hb）表位标签的克拉拉细胞分泌蛋白（CCSP）启动子的控制下，这在很大程度上限制了转基因表达的呼吸细支气管。当CCSP-mHEL/Hb转基因小鼠与识别Hb表位的N3.L2 TCR转基因小鼠杂交时，双基因后代出现致密的假滤泡淋巴细胞性细支气管周围浸润，其类似于滤泡性细支气管炎的组织学模式。活化的分泌IFN-γ和IL-17 A的CD 4 + T细胞以及B细胞聚集在气道周围。Ifng−/−和Il 17 a −/−小鼠的肺部病理学相似，表明任何一种细胞因子都足以建立慢性疾病。大量抗原特异性Treg细胞在病变中积累，受影响小鼠的Treg细胞耗竭导致疾病的间质扩散，最终证明是致命的。因此，Treg细胞起到抑制自身免疫反应的作用，导致有组织和受控的慢性病理过程，而不是进行性疾病。
In order to study regulatory T (Treg) cell control of chronic autoimmunity in a lymphoreplete host, we created and characterized a new model of autoimmune lung inflammation that targets the medium and small airways. We generated transgenic mice that express a chimeric membrane protein consisting of hen egg lysozyme (mHEL) and a hemoglobin (Hb) epitope tag under the control of the Clara cell secretory protein (CCSP) promoter, which largely limited transgene expression to the respiratory bronchioles. When CCSP-mHEL/Hb transgenic mice were crossed to N3.L2 TCR transgenic mice that recognize the Hb epitope, the bigenic progeny developed dense, pseudo-follicular lymphocytic peribronchiolar infiltrates that resembled the histological pattern of follicular bronchiolitis. Aggregates of activated IFN-γ- and IL-17A-secreting CD4+ T cells as well as B cells surrounded the airways. Lung pathology was similar in Ifng−/− and Il17a−/− mice, indicating that either cytokine is sufficient to establish chronic disease. A large number of antigen-specific Treg cells accumulated in the lesions and Treg cell-depletion in the affected mice led to an interstitial spread of the disease that ultimately proved fatal. Thus Treg cells act to restrain autoimmune responses, resulting in an organized and controlled chronic pathological process rather than a progressive disease.
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影响因子：
32.4
作者：
Fontenot, JD;Rasmussen, JP;Rudensky, AY
通讯作者：
Rudensky, AY
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
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Williams CB
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影响因子：
56.9
作者：
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通讯作者：
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影响因子：
4.4
作者：
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通讯作者：
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