Insights Into Type I and III Interferons in Asthma and Exacerbations

Abstract

Asthma is a highly prevalent, chronic respiratory disease that impacts millions of people worldwide and causes thousands of deaths every year. Asthmatics display different phenotypes with distinct genetic components, environmental causes, and immunopathologic signatures, and are broadly characterized into type 2-high or type 2-low (non-type 2) endotypes by linking clinical characteristics, steroid responsiveness, and molecular pathways. Regardless of asthma severity and adequate disease management, patients may experience acute exacerbations of symptoms and a loss of disease control, often triggered by respiratory infections. The interferon (IFN) family represents a group of cytokines that play a central role in the protection against and exacerbation of various infections and pathologies, including asthma. Type I and III IFNs in particular play an indispensable role in the host immune system to fight off pathogens, which seems to be altered in both pediatric and adult asthmatics. Impaired IFN production leaves asthmatics susceptible to infection and with uncontrolled type 2 immunity, promotes airway hyperresponsiveness (AHR), and inflammation which can lead to asthma exacerbations. However, IFN deficiency is not observed in all asthmatics, and alterations in IFN expression may be independent of type 2 immunity. In this review, we discuss the link between type I and III IFNs and asthma both in general and in specific contexts, including during viral infection, co-infection, and bacterial/fungal infection. We also highlight several studies which examine the potential role for type I and III IFNs as asthma-related therapies.

Type I Interferon Production of Plasmacytoid Dendritic Cells under Control

“…However, asthmatic patients are characterized by attenuated type I IFN production and uncontrolled Th2 response that makes them more susceptible to viral infections and infection-induced asthma exacerbations. The impaired type I IFN production might be the result of FcεRI cross-linking, which negatively effects the type I IFN pathway [268][269][270].…”

“…Inhaled corticosteroids are commonly used for the long-term treatment of asthmatic patients to resolve symptoms. However, it is important to note that these drugs can suppress type I IFN production and contribute to the onset of a Th2-dominant phenotype that makes patients more vulnerable to respiratory tract infections [270]. Therefore, type I IFN therapy could be utilized for the treatment of patients with allergic asthma and other chronic atopic diseases with Th2 dominance, in which type I IFNs could counterbalance Th2 cell-mediated inflammation.…”

“…Therefore, type I IFN therapy could be utilized for the treatment of patients with allergic asthma and other chronic atopic diseases with Th2 dominance, in which type I IFNs could counterbalance Th2 cell-mediated inflammation. Preclinical and clinical trials using type I IFN-based therapy for the treatment of atopic diseases are summarized in references [268,270] (Figure 4).…”

Large‐scale plasma proteomics can reveal distinct endotypes in chronic obstructive pulmonary disease and severe asthma

“… 36 Additional markers include INFγ, a Th1 response cytokine, critical for innate and adaptive immunity against viral infection. 37 Proteins‐F involved in the development and growth of epithelial tissue. A key protein is FGF‐9 (fibroblast growth factor 9) involved in lung development especially in regards retaining lung mesenchymal proliferation.…”

“… 36 Additional markers include INFγ, a Th1 response cytokine, critical for innate and adaptive immunity against viral infection. 37 …”