Further work will be needed to better define the development of APECs into a specialized IL-33-expressing niche. inflammatory response to environmental agents in genetically susceptible individuals is responsible for causing this type of disease. Environmental agents that may trigger asthma or COPD include allergens, tobacco and wood smoke, and microbial pathogens. Indeed, there has been considerable progress in defining how the immune system of the lungs responds to these agents. The conventional view Mestranol has been that the adaptive immune response is crucial for the type of long-term inflammation that is required to drive chronic respiratory disease. This scheme has been particularly well developed for allergic reactions, but has also been extrapolated to explain the immune responses that are induced by non-allergic stimuli3. However, an alternative view that is gaining wider acceptance is that the innate immune system also drives chronic respiratory disease (FIG. 1). This conceptual shift raises the possibility that sentinel epithelial cells and immune cells might be essential components of pathogenesis, and might represent new targets for therapeutic intervention. A particular challenge is to explain how innate immune responses, which are traditionally viewed as being transient in nature, can drive the type of long-term immune activation that is seen in the context of chronic inflammatory disease. Open in a separate window Figure 1 Adaptive and innate immune responses in chronic respiratory diseasea | Environm ental stimuli suchas respiratory viruses, allergens and/or tobacco smoke may act on genetically susceptible individuals to lead to an altered immune response, end-organ dysfunction and chronic inflammatory disease. b | An modified adaptive immune response entails antigen-presenting cells, primarily dendritic cells (DCs), that process and present antigens to memory space B FGF2 cells and T cells that travel the activation of effector immune cells (such as eosinophils and mast cells). Additional T cell subsets that regulate the adaptive immune response include T helper 17 (TH17) cells, TH9 cells and regulatory T cells (not shown). On the other hand, an modified innate immune response can involve airway epithelial cells (AECs) that activate innate immune cells, such as invariant natural killer T (iNKT) cells, M2 macrophages and innate lymphoid cells (ILCs). Effector cells or innate immune cells Mestranol then create type 2 cytokines for example, interleukin-4 (IL-4) and IL-13 that take action on end-organ cells, especially AECs, to produce excessive mucus, and on airway clean muscle mass cells (ASMCs) to manifest airway hyperreactivity, which, to varying degrees, are both characteristic of individuals with asthma and chronic obstructive pulmonary disease. With this Review, we summarize the innate immune mechanisms that regulate the development of chronic respiratory diseases, focusing on asthma and COPD. We describe the recent data that have uncovered how airway epithelial cells (AECs) and innate immune cells Mestranol contribute to the pathogenesis of airway disease, and we then clarify how these insights are becoming translated into restorative applications. We focus on the growing data that suggest a role for respiratory viral illness as a key result in for the initiation, exacerbation and progression of the immune reactions that underlie chronic airway disease. Related to this, we also focus on how long-term reprogramming of AECs may account for how the innate immune system can travel the chronic activation of immune effector cells that mediates lifelong disease. For a more detailed conversation on specific aspects of the innate immune system, we refer the reader to additional recent evaluations4C9. We conclude having a perspective on.