IL-33–Dependent Type 2 Inflammation during Rhinovirus-induced Asthma Exacerbations In Vivo
DJ Jackson, H Makrinioti, BMJ Rana… - American journal of …, 2014 - atsjournals.org
DJ Jackson, H Makrinioti, BMJ Rana, BWH Shamji, MB Trujillo-Torralbo, J Footitt…
American journal of respiratory and critical care medicine, 2014•atsjournals.orgRationale: Rhinoviruses are the major cause of asthma exacerbations; however, its
underlying mechanisms are poorly understood. We hypothesized that the epithelial cell–
derived cytokine IL-33 plays a central role in exacerbation pathogenesis through
augmentation of type 2 inflammation. Objectives: To assess whether rhinovirus induces a
type 2 inflammatory response in asthma in vivo and to define a role for IL-33 in this pathway.
Methods: We used a human experimental model of rhinovirus infection and novel airway …
underlying mechanisms are poorly understood. We hypothesized that the epithelial cell–
derived cytokine IL-33 plays a central role in exacerbation pathogenesis through
augmentation of type 2 inflammation. Objectives: To assess whether rhinovirus induces a
type 2 inflammatory response in asthma in vivo and to define a role for IL-33 in this pathway.
Methods: We used a human experimental model of rhinovirus infection and novel airway …
Rationale: Rhinoviruses are the major cause of asthma exacerbations; however, its underlying mechanisms are poorly understood. We hypothesized that the epithelial cell–derived cytokine IL-33 plays a central role in exacerbation pathogenesis through augmentation of type 2 inflammation.
Objectives: To assess whether rhinovirus induces a type 2 inflammatory response in asthma in vivo and to define a role for IL-33 in this pathway.
Methods: We used a human experimental model of rhinovirus infection and novel airway sampling techniques to measure IL-4, IL-5, IL-13, and IL-33 levels in the asthmatic and healthy airways during a rhinovirus infection. Additionally, we cultured human T cells and type 2 innate lymphoid cells (ILC2s) with the supernatants of rhinovirus-infected bronchial epithelial cells (BECs) to assess type 2 cytokine production in the presence or absence of IL-33 receptor blockade.
Measurements and Main Results: IL-4, IL-5, IL-13, and IL-33 are all induced by rhinovirus in the asthmatic airway in vivo and relate to exacerbation severity. Further, induction of IL-33 correlates with viral load and IL-5 and IL-13 levels. Rhinovirus infection of human primary BECs induced IL-33, and culture of human T cells and ILC2s with supernatants of rhinovirus-infected BECs strongly induced type 2 cytokines. This induction was entirely dependent on IL-33.
Conclusions: IL-33 and type 2 cytokines are induced during a rhinovirus-induced asthma exacerbation in vivo. Virus-induced IL-33 and IL-33–responsive T cells and ILC2s are key mechanistic links between viral infection and exacerbation of asthma. IL-33 inhibition is a novel therapeutic approach for asthma exacerbations.
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