Robinson Marcus J, Prout Melanie, Mearns Helen, Kyle Ryan, Camberis Mali, Forbes-Blom Elizabeth E, Paul William E, Allen Christopher D C, Le Gros Graham
Malaghan Institute of Medical Research, Wellington 6242, New Zealand.
Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143.
J Immunol. 2017 Mar 1;198(5):1815-1822. doi: 10.4049/jimmunol.1601434. Epub 2017 Jan 23.
Polymorphisms in genes involved in IL-4 responses segregate with allergic disease risk and correlate with IgE levels in humans, and IL-4 promotes IgE and IgG1 Ab production against allergens in mice. We report that mice with only one intact gene copy are significantly impaired in their ability to make specific IgE responses against allergens, whereas IgG1 responses to allergens remain unaffected. -hemizygosity also resulted in a modest but detectable drop in IL-4 production by CD4 T cells isolated from lymph nodes and prevented IgE-dependent oral allergen-induced diarrhea. We conclude that a state of haploinsufficiency for the gene locus is specifically relevant for IL-4-dependent IgE responses to allergens with the amount of IL-4 produced in the hemizygous condition falling close to the threshold required for switching to IgE production. These results may be relevant for how polymorphisms in genes affecting IL-4 responses influence the risk of IgE-mediated allergic disease in humans.
参与白细胞介素-4（IL-4）反应的基因多态性与过敏性疾病风险相关联，并与人类的免疫球蛋白E（IgE）水平相关，而且IL-4可促进小鼠针对过敏原产生IgE和免疫球蛋白G1（IgG1）抗体。我们报告称，只有一个完整基因拷贝的小鼠在针对过敏原产生特异性IgE反应的能力上显著受损，而对过敏原的IgG1反应则不受影响。半合子状态还导致从淋巴结分离出的CD4 T细胞产生的IL-4出现适度但可检测到的下降，并阻止了IgE依赖的口服过敏原诱导的腹泻。我们得出结论，基因座的单倍剂量不足状态与针对过敏原的IL-4依赖的IgE反应特别相关，半合子状态下产生的IL-4量接近转换为IgE产生所需的阈值。这些结果可能与影响IL-4反应的基因多态性如何影响人类IgE介导的过敏性疾病风险有关。
