T1-T2 Interplay in the Complex Immune Landscape of Severe Asthma

Abstract

Asthma is orchestrated by an aberrant immune response involving a complex interplay between multiple inflammatory cell types. An increase in Th2 cells in the asthmatic airway is a hallmark of asthma, and biologics blocking their effector functions have been life-changing for many severe asthma patients who poorly respond to immunosuppression by corticosteroids. However, studies in the past decade have highlighted not only other cell types that also produce Th2 cytokines boosting the Type 2/T2 phenotype but also a heightened IFN-γ response, primarily from T cells, referred to as a Type 1/T1 immune response. Data derived from studies of immune cells in the airways and mouse models of severe asthma suggest a role of IFN-γ in corticosteroid resistance, airway hyperreactivity, and also airway remodeling via effects on other cell types including mast cells, eosinophils, airway epithelial cells, and airway smooth muscle cells. The simultaneous presence of T1 and T2 immune responses is detectable in the sickest of asthma patients in whom corticosteroids suppress the T2 but not the T1 response. This article has reviewed our current understanding of the complex T1–T2 interplay in severe asthma highlighting mediators that impact both arms which may be targeted alone or in combination for disease alleviation.