Critical role of caspase-8–mediated IL-1 signaling in promoting Th2 responses during asthma pathogenesi

Allergic asthma is a heterogeneous, chronic inflammatory disease characterized by hyperresponsiveness, smooth muscle hypertrophy, obstruction and infiltration of inflammatory cells in the airway. T lymphocytes, particularly Th2 cells and Th2-type cytokines, such as IL-4, IL-5, and IL-13, are immunological signatures of allergic immune responses to inhaled antigens1, 2. Accumulating evidence points to the involvement of proinflammatory cytokines within the IL-1 family, specifically IL-1α and IL-1β, in Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: aTo whom correspondence should be addressed: Thirumala-Devi Kanneganti, Department of Immunology, MS 351, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN , Tel: (901) 595-3634; Fax: (901) 595-5766, . DISCLOSURE The authors declared no conflict of interest. HHS Public Access Author manuscript Mucosal Immunol. Author manuscript; available in PMC 2017 February 01. Published in final edited form as: Mucosal Immunol. 2017 January ; 10(1): 128–138. doi:10.1038/mi.2016.25. Author Manuscript Author Manuscript Author Manuscript Author Manuscript development of pulmonary Th2 immune responses and asthma3–5. Patients with asthma often have excessive production of IL-1 cytokines6 . In addition, administration of active human IL-1β to the mouse trachea induces airway inflammation and tissue remodeling7 . The involvement of IL-1 in asthmatic diseases is further supported by the observation that genetic disruption of the IL-1 signaling pathway strongly attenuates allergic disease in murine models of asthma4, 8. Moreover, recent studies revealed that IL-1 cytokines secreted in response to inhaled allergens can instruct pulmonary dendritic cells to induce Th2 responses and directly promote the activation of Th2 cells9, 10. Collectively, results from these studies suggest that IL-1 is one of the apical signals of the cytokine cascade that drives dendritic cell activation and Th2 immunity in response to inhaled allergens. Despite important advances in understanding the crucial role of IL-1 cytokines in the genesis of allergic asthma, the mechanism of IL-1 production that contributes to inflammatory airway disease remains unknown. Certain members of the IL-1 family, including IL-1β and IL-18, require proteolyti