Mouse models have played significant roles in our understanding of the immunological mechanism(s) leading to the development of allergic airway inflammation. However, various strains of mice respond differently in these models, and there are more than a few examples of gene knockouts that display contrasting phenotypes in different backgrounds 
. This is exemplified by the known differences in behavior between C57BL/6 and BALB/c backgrounds in models of allergic airway inflammation 
. For example, analysis of IL-5 or T-bet knockouts, or the absence of eosinophils, has revealed differences in responses dependent on whether they are on a C57BL/6 or BALB/c background 
. As a result, it is currently difficult to evaluate without ambiguity, the roles of specific molecules in this disease.
In theoretical and empirical infectious disease models, the concept of tolerance (T
) and resistance (R
) has been developed 
. This concept states that animals that are infected with a pathogen may vary in their response, which can be one of complete resistance, i.e. animals are resistant to developing symptoms of an infection. Alternatively, animals can vary in tolerance, such that the symptoms that develop after infection can be mild, and such animals would be said to have a high tolerance, while animals that have severe symptoms would be said to have low tolerance 
. However, these responses do not address whether animals are susceptible, i.e. able to be infected by the pathogen, or the mechanisms behind their responses. In this case, one can surmise that a tolerant animal mobilizes immune mechanisms to blunt the pathological effects of the infection and so has varying degrees of tolerance. By contrast, a resistant animal may either rapidly reduce pathogen infection, or rapidly down modulate immune mediated pathological responses such that they are viewed as resistant (to developing symptoms). In both cases, the mechanisms can be potentially traced to the presence of robust immune responses.
Here we suggest that similar models could be applied to study diseases like allergic airway inflammation, in which the trigger for disease is not necessarily an infectious agent. In this case, we propose that animals that have mild symptoms of the disease have low susceptibility (Saai, S for susceptibility with subscript aai to denote the disease, allergic airway inflammation, being analyzed), while animals with elevated symptoms have high susceptibility. Animals with no symptoms are resistant (Raai, R for resistant with subscript aai to denote the disease being analyzed). In the first case of animals with varying degrees of susceptibility, this may be related to the nature and intensity of the immune mediated pathology, while in the second case, this could be related to either a lack of response, or strong down modulation of the immune mediated pathology. While all susceptible animals develop symptoms, analyzing the degrees of susceptibility could allow for discrimination of responses that is not currently appreciated with simple scoring of susceptible and resistant. Decreasing susceptibility (e.g. by pharmaceutical approaches) may be enough to significantly reduce pathology.
We suggest that strain specific differences in responses in allergic airway inflammation models may be due to differences in degrees of susceptibility (degrees of response), or resistance (lack of response or strong down modulation of the immune mediated pathology). It would also be useful to be able to categorize the effects of gene knockouts based on these two parameters, rather than merely susceptible and resistant, since targeting such genes could be an approach to decrease susceptibility and symptoms. In this case, an animal with high Saai would develop allergic airway inflammation at low doses of allergen, while one with low Saai would require higher doses. By contrast, an animal that is resistant (Raai) would not develop symptoms regardless of allergen dose. However, thresholds for allergen exposure and development of disease would have to be established. Experiments that vary antigenic exposure could be used to determine whether strains or gene knockouts have increased or decreased tolerance, or resistance.
Ovalbumin (OVA) sensitization is a popular model for allergic airway inflammation. This model is well established and results in the development of allergic airway inflammation 
. OVA is initially administered with the adjuvant aluminum hydroxide (Alum) via intraperitoneal injections. The mice are then challenged with antigen OVA by respiratory exposure which triggers the onset of symptoms of the disease 
. However, this model has limitations, including the fact that it may not reflect natural routes of allergen exposure. In addition, long term exposure to OVA results in the development of tolerance, thus reducing the flexibility in experiments that seek to address varying antigen concentrations 
. The house dust mite (HDM) species Dermatophagoides pteronyssinus
is a perennial indoor allergen and it is known to exacerbate the symptoms of allergic airway inflammation in patients. HDM causes airway inflammation in at least 10 percent of the general population, and it is known to exacerbate asthmatic symptoms in 90 percent of humans 
. In mouse models, exposure to whole HDM extracts results in the development of allergic airway inflammation, even without prior sensitization (as is required for OVA) 
. In addition, chronic exposure does not result in the development of tolerance as is typically observed with OVA 
The tyrosine kinase Interleukin-2 Inducible T cell kinase (Itk) plays an important role in the development of Th2 type responses 
. Using mouse models of allergic airway inflammation as models of allergic asthma, we have previously shown that Itk plays an important role in the induction of Th2 and Th17 responses that regulate the development of this disease 
. On the C57BL/6 background, we have reported that the absence of Itk abrogates the development of various symptoms associated with the model of allergic asthma such as airway hyperresponsiveness, mucous production, lymphocyte infiltration and inflammatory cytokine production 
. We previously used the well established model allergen, ovalbumin (OVA) in these studies, however, as mentioned previously, there are some limitations to this model.
Here we have used HDM extracts in a model of allergic airway inflammation, along with WT and Itk null mice on both C57BL/6 and BALB/c background, to determine whether mice lacking Itk are resistant or have reduced susceptibility to the development of allergic airway inflammation. We developed a mathematical model to determine resistance versus susceptibility, and show that as previously suggested, C57BL/6 mice exhibit reduced susceptibility to developing allergic airway inflammation compared to BALB/c mice. However, on the C57BL/6 background, the absence of Itk results in resistance, but on the BALB/c background results in reduced susceptibility. Our approach also provides a generalized approach to determining whether the absence of specific genes in mice affect susceptibility to developing allergic airway inflammation.