Modulating local airway immune responses to treat allergic asthma: lessons from experimental models and human studies

With asthma affecting over 300 million individuals world-wide and estimated to affect 400 million by 2025, developing effective, long-lasting therapeutics is essential. Allergic asthma, where Th2-type immunity plays a central role, represents 90% of child and 50% of adult asthma cases. Research based largely on animal models of allergic disease have led to the generation of a novel class of drugs, so-called biologicals, that target essential components of Th2-type inflammation. Although highly efficient in subclasses of patients, these biologicals and other existing medication only target the symptomatic stage of asthma and when therapy is ceased, a flare-up of the disease is often observed. Therefore, it is suggested to target earlier stages in the inflammatory cascade underlying allergic airway inflammation and to focus on changing and redirecting the initiation of type 2 inflammatory responses against allergens and certain viral agents. This focus on upstream aspects of innate immunity that drive development of Th2-type immunity is expected to have longer-lasting and disease-modifying effects, and may potentially lead to a cure for asthma. This review highlights the current understanding of the contribution of local innate immune elements in the development and maintenance of inflammatory airway responses and discusses available leads for successful targeting of those pathways for future therapeutics.