The Innate Lymphoid System Is a Critical Player in the Manifestation of Mucoinflammatory Airway Disease in Mice

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Innate lymphoid and adaptive immune cells are known to regulate epithelial responses, including mucous cell metaplasia (MCM), but their roles in mucoinflammatory airway diseases, such as cystic fibrosis, remain unknown. transgenic (-Tg) mice, which recapitulate cystic fibrosis-like mucoinflammatory airway disease, deficient in innate lymphoid ( knockout mice [ ]), adaptive immune ( knockout mice [ ]), or both systems ( / ), were employed to investigate their respective contributions in the pathogenesis of mucoinflammatory airway disease. As previously reported, immunocompetent Tg juveniles exhibited spontaneous neonatal bacterial infections with robust mucoinflammatory features, including elevated expression of -associated markers accompanied by MCM, elevated MUC5B expression, and airway mucus obstruction. The bacterial burden was increased in Tg juveniles but returned to significantly lower levels in / /Tg juveniles. Mechanistically, this improvement reflected reduced production of adaptive immunity-derived IL-10 and, in turn, increased activation of macrophages. Although all the mucoinflammatory features were comparable between the immunocompetent Tg and /Tg juveniles, the /Tg and / /Tg juveniles exhibited suppressed expression levels of markers, diminished MCM, suppressed MUC5B expression, and reduced mucus obstruction. Collectively, these data indicate that, in the context of airway mucus obstruction, the adaptive immune system suppresses antibacterial macrophage activation, whereas the innate lymphoid system contributes to MCM, mucin production, and mucus obstruction.

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Journal of immunology (Baltimore, Md. : 1950)

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