Thus the pathophysiology of allergic asthma is traditionally explained by mast celland/or Th2 cell-mediated airway inflammation, which is a manifestation of the acquired immune response. On the other hand, recent studies have identified various other important molecules associated with phenotypes of asthma, including tumor necrosis factor (TNF)[2, 3] , thymic stromal lymphoprotein [4, 5] , interleukin (IL)-33 [6, 7] and IL-25 [8, 9] . TNFis produced mainly in macrophages and mast cells, and thymic stromal lymphoprotein, IL-33 and IL-25 are mainly from epithelial cells and various leukocytes. Those molecules are considered to play roles in the innate immune response. In order to understand novel pathophysiological mechanisms of asthma, a recent trend has been toward the generation of novel animal models, including asthma associated with both acquired and innate immunity, severe asthma such as steroid-resistant phenotypes [10–12] , neutrophilic asthma [13, 14] and the viral exacerbation of allergic inflammation [15, 16] . It is believed that these new asthma models will lead to the development of new strategies for asthma. In this issue of International Archives of Allergy and Immunology , Kim et al. [17] present a well-conducted murine asthma model of AHR, where part of the mechanism reported was TNF-mediated airway inflammation. They observed detailed time-course changes in the occurrence of AHR after antigen (ovalbumin) challenge in According to established knowledge, the mechanisms of allergic asthma are as follows: when an inhaled allergen penetrates the airway epithelium, it is detected by dendritic cells, which migrate to the lymph node and present the processed antigen to T cells, and B cells start to produce antigen-specific immunoglobulin E (IgE). IgE binds to Fc  receptors on a variety of cell types including mast cells and basophils. When an allergic individual is subsequently exposed to the specific allergen, the allergen binds to the specific IgE on the cells, causing activation of mast cells and basophils to release chemical mediators, such as histamine, arachidonic acid metabolites and proteases into the airway tissue. These mediators cause an early asthmatic response, which is an airway obstruction induced within 30 min after allergen exposure. There is also a specific population of asthmatic subjects which exhibits a late asthmatic response, i.e. an airway obstruction triggered several hours after allergen challenge and persisting for a relatively long time. The late asthmatic response has been thought to be based on airway inflammation orchestrated by Th2 cells and eosinophils [1] . In addition to the early and late asthmatic responses, Th2-biased airway inflammation leads to airway hyperresponsiveness (AHR) to nonspecific stimuli and structural remodeling of airway tissues. Various experimental models reproduce these phenotypes of asthma. Published online: September 25, 2012