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Title: Caspase-11 regulates lung in response to house dust mites
Authors: Abu Khweek, Arwa 
Keywords: Asthma;Lung disorders;House dust mites - Health aspects;Allergic sensitization
Issue Date: 2021
Abstract: Asthma is an inammatory lung disorder characterized by mucus hypersecretion, cellular inltration, and bronchial hyper-responsiveness. House dust mites (HDM) are the most prevalent cause of allergic sensitization. Canonical and noncanonical inammasomes are multiprotein complexes that assemble in response to pathogen or danger-associated molecular patterns (PAMPs or DAMPs). Murine caspase-11 engages the noncanonical inammasome. We addressed the role of caspase-11 in mediating host responses to HDM and subsequent allergic inammation using caspase-11 −/− mice, which lack caspase11 while express caspase-1. We found that HDM induce caspase-11 expression in vitro. The presence of IL-4 and IL-13 promotes caspase-11 expression. Additionally, caspase-11 −/− macrophages show reduced release of (KC, IL-6 and IL-12) cytokines, and express lower levels of costimulatory molecules (e.g., CD40, CD86 and MHCII) in response to HDM stimulation. Notably, HDM sensitization of caspase-11 −/− mice resulted in similar levels of IgE responses and hypothermia in response to nasal HDM challenge compared to WT. However, analysis of cell numbers and cytokines in bronchiolar alveolar uid (BALF), as well as histological lung tissue showed altered inammatory responses and reduced neutrophilia in the airways of the caspase-11 −/− mice. These findings indicate that caspase-11 regulates airway inammation in response to HDM exposure.
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