Institute for Immunology, Medical Center, Johannes Gutenberg University, Mainz D-55131, Germany.
J Immunol. 2011 Jun 15;186(12):7225-31. doi: 10.4049/jimmunol.1100676. Epub 2011 May 13.
Mast cell-deficient mice are a key for investigating the function of mast cells in health and disease. Allergic airway disease induced as a Th2-type immune response in mice is employed as a model to unravel the mechanisms underlying inception and progression of human allergic asthma. Previous work done in mast cell-deficient mouse strains that otherwise typically mount Th1-dominated immune responses revealed contradictory results as to whether mast cells contribute to the development of airway hyperresponsiveness and airway inflammation. However, a major contribution of mast cells was shown using adjuvant-free protocols to achieve sensitization. The identification of a traceable genetic polymorphism closely linked to the Kit(W-sh) allele allowed us to generate congenic mast cell-deficient mice on a Th2-prone BALB/c background, termed C.B6-Kit(W-sh). In accordance with the expectations, C.B6-Kit(W-sh) mice do not develop IgE- and mast cell-dependent passive cutaneous anaphylaxis. Yet, unexpectedly, C.B6-Kit(W-sh) mice develop full-blown airway inflammation, airway hyperresponsiveness, and mucus production despite the absence of mast cells. Thus, our findings demonstrate a major influence of genetic background on the contribution of mast cells in an important disease model and introduce a novel strain of mast cell-deficient mice.
缺乏肥大细胞的小鼠是研究肥大细胞在健康和疾病中的功能的关键。作为一种模型，以 Th2 型免疫反应诱导的过敏性气道疾病被用来揭示人类过敏性哮喘发病和进展的机制。在其他通常产生 Th1 优势免疫反应的缺乏肥大细胞的小鼠品系中进行的先前研究结果表明，肥大细胞是否有助于气道高反应性和气道炎症的发展存在矛盾。然而，使用无佐剂方案实现致敏显示了肥大细胞的主要作用。鉴定与 Kit(W-sh)等位基因紧密连锁的可追踪遗传多态性，使我们能够在 Th2 倾向的 BALB/c 背景上生成同源性缺乏肥大细胞的小鼠，称为 C.B6-Kit(W-sh)。与预期一致，C.B6-Kit(W-sh) 小鼠不会产生 IgE 和肥大细胞依赖性被动皮肤过敏反应。然而，出人意料的是，尽管缺乏肥大细胞，C.B6-Kit(W-sh) 小鼠仍会发生完全的气道炎症、气道高反应性和黏液产生。因此，我们的研究结果表明遗传背景对重要疾病模型中肥大细胞的作用有重大影响，并介绍了一种新型缺乏肥大细胞的小鼠品系。
