Temperature-driven Modulation of Airway Epithelial Cell Composition and Host Responses: Implications for Chronic Obstructive Pulmonary Disease (COPD)

Abstract

The cellular composition of the airway epithelium follows a gradient along the respiratory tract. The mechanisms governing these spatial patterns are not fully understood. One possible cue is temperature, which also follows a gradient along the respiratory tree, and we aimed to explore a potential relation. We assessed the impact of temperature on cellular composition of the airway epithelium and investigated its functional consequences. To this end, primary bronchial epithelial cell cultures were differentiated at the air-liquid interface for five weeks at 37°C (small airway region), after which part of the cultures were changed to 33°C (nasal region) for 3, 7 or 14 days and subsequently assessed for cellular composition. In addition, we exposed cultures after 7 days of temperature change, to either whole cigarette smoke (WCS) or Poly(I:C) for respectively 4h or 6h and 24h to examine host responses. Preliminary findings indicate that switching to 33°C caused a significant decrease in FOXJ1 (ciliated cells) gene expression and a significant increase in MUC5AC (goblet cells) expression after 7 days. In addition, HMOX1 expression in response to WCS was only significantly increased in 37°C cultures, while interferon lambda expression following Poly(I:C) stimulation was significantly higher in 33°C cultures compared to those at 37°C. Ongoing experiments are focused on assessing effects on antimicrobial peptide expression and mucociliary clearance. Elucidating the intricate relationship between temperature, airway epithelial cell composition and host defense, may be relevant for understanding airway diseases.

Authors 8

1. Dennis K. Ninaber Aachen 1PulmoScience Lab Dept of Pulmonology, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   1PulmoScience Lab, Department of Pulmonology, Leiden University Medical Center, Leiden, Netherlands

2. Melissa Thaler Aachen 2Department of Medical Microbiology

   Leiden University Medical Center

   Affiliation as printed

   2Department of Medical Microbiology, Leiden University Medical Center, Leiden, Netherlands

3. Ying Wang Aachen 1PulmoScience Lab Dept of Pulmonology, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   1PulmoScience Lab, Department of Pulmonology, Leiden University Medical Center, Leiden, Netherlands

4. Martijn J. van Hemert Aachen 2Department of Medical Microbiology

   Leiden University Medical Center

   Affiliation as printed

   2Department of Medical Microbiology, Leiden University Medical Center, Leiden, Netherlands

5. Janna C. Nawroth

   Helmholtz Munich · Institute of Biological and Medical Imaging

   Affiliation as printed

   3Helmholtz Pioneer Campus and Institute of Biological and Medical Imaging, Helmholtz Zentrum München, Munich, Germany

6. Pieter Sicco Hiemstra Aachen 1PulmoScience Lab Dept of Pulmonology, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   1PulmoScience Lab, Department of Pulmonology, Leiden University Medical Center, Leiden, Netherlands

7. Alen Faiz

   University of Technology Sydney

   Affiliation as printed

   4University of Technology Sydney, Respiratory Bioinformatics and Molecular Biology (RBMB), School of Life Sciences, Sidney, Australia

8. Anne M. van der Does Aachen 1PulmoScience Lab Dept of Pulmonology, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   1PulmoScience Lab, Department of Pulmonology, Leiden University Medical Center, Leiden, Netherlands