阻抑蛋白---T细胞的细胞内抗原-1（TIA-1）是Th2和Th17反应的一个关键调节子，能促进屋尘
2012/07/05
摘要
T细胞的细胞内抗原-1（TIA-1）是一个直接的阻抑蛋白，它能阻止促炎细胞因子和酶的产生。本研究在屋尘螨（户尘螨）过敏原提取物（Df）诱导的小鼠肺炎症模型中，评价TIA-1的作用。如采用低剂量Df鼻内给予进行激发试验，与野生型同窝小鼠相比，TIA-1蛋白缺陷（Tia-1-/-）小鼠气道和组织中嗜酸性粒细胞数量更多、肺支气管血管束浸润更严重、杯状细胞化生更明显。Tia-1-/-小鼠血清同时具有较高水平的Df特异性IgE和IgG1，体外刺激Tia-1-/-淋巴结细胞和脾细胞能转录和释放更多的Th2/Th17细胞因子。为了评价TIA-1作用的位点，我们检测了骨髓嵌合体针对Df的反应。结果显示，TIA-1能作用于造血细胞和非造血细胞，抑制肺部炎症。同时TIA-1也是体内一个抗原介导的肺部炎症负向调节子。因此，TIA-1可能是支气管哮喘致病的一个重要参与者。
（苏楠 审校）
Immunol Lett. 2012 Apr 15. [Epub ahead of print]
The translational repressor T-cell intracellular antigen-1 (TIA-1) is a key modulator of Th2 and Th17 responses driving pulmonary inflammation induced by exposure to house dust mite.
Simarro M, Giannattasio G, Xing W, Lundequist EM, Stewart S, Stevens RL, Orduña A, Boyce JA, Anderson PJ.
Source
Department of Medicine, Harvard Medical School, USA; Division of Rheumatology, Immunology and Allergy, Brigham and Women’s Hospital, Boston, MA 02115, USA; Unidad de Investigación del Hospital Clínico Universitario de Valladolid, Spain; Departamento de Microbiología, Facultad de Medicina de Valladolid, Spain.
Abstract
T-cell intracellular antigen-1 (TIA-1) is a translational repressor that dampens the production of proinflammatory cytokines and enzymes. In this study we investigated the role of TIA-1 in a mouse model of pulmonary inflammation induced by exposure to the allergenic extract (Df) of the house dust mite Dermatophagoides farinae. When intranasally challenged with a low dose of Df, mice lacking TIA-1 protein (Tia-1(-/-)) showed more severe airway and tissue eosinophilia, infiltration of lung bronchovascular bundles, and goblet cell metaplasia than wild-type littermates. Tia-1(-/-) mice also had higher levels of Df-specific IgE and IgG(1) in serum and ex vivo restimulated Tia-1(-/-) lymph node cells and splenocytes transcribed and released more Th2/Th17 cytokines. To evaluate the site of action of TIA-1, we studied the response to Df in bone marrow chimeras. These experiments revealed that TIA-1 acts on both hematopoietic and non-hematopoietic cells to dampen pulmonary inflammation. Our results identify TIA-1 as a negative regulator of allergen-mediated pulmonary inflammation in vivo. Thus, TIA-1 might be an important player in the pathogenesis of bronchial asthma.
Immunol Lett. 2012 Apr 15. [Epub ahead of print]
T细胞的细胞内抗原-1（TIA-1）是一个直接的阻抑蛋白，它能阻止促炎细胞因子和酶的产生。本研究在屋尘螨（户尘螨）过敏原提取物（Df）诱导的小鼠肺炎症模型中，评价TIA-1的作用。如采用低剂量Df鼻内给予进行激发试验，与野生型同窝小鼠相比，TIA-1蛋白缺陷（Tia-1-/-）小鼠气道和组织中嗜酸性粒细胞数量更多、肺支气管血管束浸润更严重、杯状细胞化生更明显。Tia-1-/-小鼠血清同时具有较高水平的Df特异性IgE和IgG1，体外刺激Tia-1-/-淋巴结细胞和脾细胞能转录和释放更多的Th2/Th17细胞因子。为了评价TIA-1作用的位点，我们检测了骨髓嵌合体针对Df的反应。结果显示，TIA-1能作用于造血细胞和非造血细胞，抑制肺部炎症。同时TIA-1也是体内一个抗原介导的肺部炎症负向调节子。因此，TIA-1可能是支气管哮喘致病的一个重要参与者。
（苏楠 审校）
Immunol Lett. 2012 Apr 15. [Epub ahead of print]
The translational repressor T-cell intracellular antigen-1 (TIA-1) is a key modulator of Th2 and Th17 responses driving pulmonary inflammation induced by exposure to house dust mite.
Simarro M, Giannattasio G, Xing W, Lundequist EM, Stewart S, Stevens RL, Orduña A, Boyce JA, Anderson PJ.
Source
Department of Medicine, Harvard Medical School, USA; Division of Rheumatology, Immunology and Allergy, Brigham and Women’s Hospital, Boston, MA 02115, USA; Unidad de Investigación del Hospital Clínico Universitario de Valladolid, Spain; Departamento de Microbiología, Facultad de Medicina de Valladolid, Spain.
Abstract
T-cell intracellular antigen-1 (TIA-1) is a translational repressor that dampens the production of proinflammatory cytokines and enzymes. In this study we investigated the role of TIA-1 in a mouse model of pulmonary inflammation induced by exposure to the allergenic extract (Df) of the house dust mite Dermatophagoides farinae. When intranasally challenged with a low dose of Df, mice lacking TIA-1 protein (Tia-1(-/-)) showed more severe airway and tissue eosinophilia, infiltration of lung bronchovascular bundles, and goblet cell metaplasia than wild-type littermates. Tia-1(-/-) mice also had higher levels of Df-specific IgE and IgG(1) in serum and ex vivo restimulated Tia-1(-/-) lymph node cells and splenocytes transcribed and released more Th2/Th17 cytokines. To evaluate the site of action of TIA-1, we studied the response to Df in bone marrow chimeras. These experiments revealed that TIA-1 acts on both hematopoietic and non-hematopoietic cells to dampen pulmonary inflammation. Our results identify TIA-1 as a negative regulator of allergen-mediated pulmonary inflammation in vivo. Thus, TIA-1 might be an important player in the pathogenesis of bronchial asthma.
Immunol Lett. 2012 Apr 15. [Epub ahead of print]
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