Immunomodulation in Cystic Fibrosis: Why and How?

• Type of Material: Article
• Authors: Vincent D. Giacalone, Emory University; Brian S. Dobosh, Emory University; Amit Gaggar, University of Alabama Birmingham; Rabindra Tirouvanziam, Emory University; Camilla Margaroli, University of Alabama Birmingham
• Language: English
• Date: 2020-05-01
• Publisher: MDPI
• Publication Version: Final Published Version
• Copyright Statement: © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3390/ijms21093331
• Title of Journal or Parent Work: International Journal of Molecular Sciences
• Volume: 21
• Issue: 9
• Grant/Funding Information: This research was funded by the UAB Research Development Program Postdoctoral Fellowship (to C.M.) as funded by the US CF Foundation Research Development Program (ROWE19R0), by the National Institutes of Health (NIH, USA) R01 HL102371 to AG, and by the US CF Foundation Basic Research Program (TIROUV17G0 and TIROUV19G0).
• Keywords: Histamine release; immunotherapy; lung disease; Epithelial cells; Allergic bronchopulmonary aspergillosis; Transmembrane conductance regulator; Neutrophil elastase; proteases; cystic fibrosis; In-vitro; Life Sciences & Biomedicine; Chemistry, Multidisciplinary; Science & Technology; Case series; Chemistry; Biochemistry & Molecular Biology; Toll-like receptors; Lung disease; inflammation; Physical Sciences
• Research Categories: Chemistry, Biochemistry; Biology, Molecular; Health Sciences, Immunology

Abstract

Cystic fibrosis (CF) lung disease is characterized by unconventional mechanisms of inflammation, implicating a chronic immune response dominated by innate immune cells. Historically, therapeutic development has focused on the mutated cystic fibrosis transmembrane conductance regulator (CFTR), leading to the discovery of small molecules aiming at modulating and potentiating the presence and activity of CFTR at the plasma membrane. However, treatment burden sustained by CF patients, side effects of current medications, and recent advances in other therapeutic areas have highlighted the need to develop novel disease targeting of the inflammatory component driving CF lung damage. Furthermore, current issues with standard treatment emphasize the need for directed lung therapies that could minimize systemic side effects. Here, we summarize current treatment used to target immune cells in the lungs, and highlight potential benefits and caveats of novel therapeutic strategies.