Nucleotide oligomerization domain 1 ligation suppressed murine allergen-specific T-cell proliferation and airway hyperresponsiveness.
Nucleotide oligomerization domain 1 ligation suppressed murine allergen-specific T-cell proliferation and airway hyperresponsiveness.
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DOI：
10.1165/rcmb.2013-0333oc
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发表时间：
2014-05
影响因子：
6.4
通讯作者：
C. Tabeling;H. Scheer;Stefanie M. Schönrock;F. Runge;B. Gutbier;J. Lienau;E. Hamelmann;B. Opitz;N. Suttorp;K. Mayer;G. Behrens;T. Tschernig;M. Witzenrath
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文献类型：
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作者：
C. Tabeling;H. Scheer;Stefanie M. Schönrock;F. Runge;B. Gutbier;J. Lienau;E. Hamelmann;B. Opitz;N. Suttorp;K. Mayer;G. Behrens;T. Tschernig;M. Witzenrath
胞质核苷酸寡聚结构域（NOD）样受体NOD1和NOD2在包括肺炎衣原菌在内的病原体的细胞内识别中起着重要作用，但它们对过敏原诱导的气道炎症的影响知之甚少。在BALB/c小鼠中，我们观察到在卵清蛋白（OVA）全身致敏前感染肺炎球菌和局部暴露于OVA气道可降低气道高反应性（AHR）。因此，在每次致敏或气道刺激前6小时给予NOD1激动剂FK156和NOD2激动剂muramyl二肽对AHR、ova特异性血浆免疫球蛋白、支气管肺泡灌洗液差异和细胞因子的影响进行了评估。分离fk156处理小鼠的脾脏树突状细胞，与DO11.10小鼠的OVA特异性T细胞共培养，并在OVA再刺激后定量T细胞增殖。研究了fk156处理和ova暴露的DO11.10小鼠肺和淋巴结内t细胞的增殖情况。FK156，而不是muramyl二肽，降低AHR和肺嗜酸性粒细胞浸润，如果在卵细胞致敏或攻击前给予，而t -辅助性（Th）2细胞因子没有减少。与溶剂处理的对照组相比，fk156处理小鼠的树突状细胞引起的ova特异性t细胞增殖较少。同样，FK156治疗后，肺组织中抗原特异性t细胞活化减少。我们得出结论，NOD1激活降低了过敏原诱导的肺部炎症的AHR，这伴随着过敏原特异性t细胞增殖的减少。
The cytosolic nucleotide oligomerization domain (NOD)-like receptors NOD1 and NOD2 are important contributors to the intracellular recognition of pathogens including Chlamydophila pneumoniae, but little is known about their influence on allergen-induced airway inflammation. In BALB/c mice, we observed that infection with C. pneumoniae before systemic sensitization with ovalbumin (OVA) and local OVA airway exposure diminished airway hyperresponsiveness (AHR). Thus, the impact of the NOD1 agonist FK156 and the NOD2 agonist muramyl dipeptide given 6 hours before each sensitization or airway challenge was evaluated regarding AHR, OVA-specific plasma immunoglobulins, bronchoalveolar lavage fluid differentials, and cytokines. Spleen dendritic cells of FK156-treated mice were isolated and cocultured with OVA-specific T cells isolated from DO11.10 mice, and T-cell proliferation was quantified after OVA restimulation. T-cell proliferation was investigated in vivo in lungs and lymph nodes of FK156-treated and OVA-exposed DO11.10 mice. FK156, but not muramyl dipeptide, reduced AHR and pulmonary eosinophilic infiltration if given before OVA sensitization or challenge, whereas T-helper (Th)2 cytokines were not diminished. Dendritic cells from FK156-treated mice evoked less OVA-specific T-cell proliferation as compared with solvent-treated controls. Similarly, antigen-specific T-cell activation in lung tissue was diminished after FK156 treatment. We conclude that NOD1 activation reduced AHR in allergen-induced lung inflammation, which was accompanied by a reduction of allergen-specific T-cell proliferation.