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

Authors

Brandon W. Lewis, Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803.
Ishita Choudhary, Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803.
Kshitiz Paudel, Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803.
Yun Mao, Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803.
Rahul Sharma, National Hansen's Disease Program, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803.
Yong Wang, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294; and.
Jessy S. Deshane, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294; and.
Richard C. Boucher, Marsico Lung Institute/University of North Carolina Cystic Fibrosis Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
Sonika Patial, Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803.
Yogesh Saini, Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803; ysaini@lsu.edu.

Document Type

Article

Publication Date

9-15-2020

Abstract

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.

Publication Source (Journal or Book title)

Journal of immunology (Baltimore, Md. : 1950)

First Page

1695

Last Page

1708

Recommended Citation

Lewis, B. W., Choudhary, I., Paudel, K., Mao, Y., Sharma, R., Wang, Y., Deshane, J. S., Boucher, R. C., Patial, S., & Saini, Y. (2020). The Innate Lymphoid System Is a Critical Player in the Manifestation of Mucoinflammatory Airway Disease in Mice. Journal of immunology (Baltimore, Md. : 1950), 205 (6), 1695-1708. https://doi.org/10.4049/jimmunol.2000530