Highway to heal: Influence of altered extracellular matrix on infiltrating immune cells during acute and chronic lung diseases

Mugdha M Joglekar; Mehmet Nizamoglu; YiWen Fan; Sai Sneha Priya Nemani; Markus Weckmann; Simon D Pouwels; Irene H Heijink; Barbro N Melgert; Janesh Pillay; Janette K Burgess

doi:10.3389/fphar.2022.995051

Highway to heal: Influence of altered extracellular matrix on infiltrating immune cells during acute and chronic lung diseases

Front Pharmacol. 2022 Nov 3:13:995051. doi: 10.3389/fphar.2022.995051. eCollection 2022.

Authors

Mugdha M Joglekar^{1

2}, Mehmet Nizamoglu^{1

2}, YiWen Fan^{1

2}, Sai Sneha Priya Nemani^{3

4}, Markus Weckmann^{3

4}, Simon D Pouwels^{1

2

5}, Irene H Heijink^{1

2

5}, Barbro N Melgert^{2

6}, Janesh Pillay^{2

7}, Janette K Burgess^{1

2

8}

Affiliations

¹ University of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, Groningen, Netherlands.
² University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, Netherlands.
³ Department of Paediatric Pneumology &Allergology, University Children's Hospital, Schleswig-Holstein, Campus Lübeck, Germany.
⁴ Epigenetics of Chronic Lung Disease, Priority Research Area Chronic Lung Diseases; Leibniz Lung Research Center Borstel; Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), Germany.
⁵ University of Groningen, University Medical Center Groningen, Department of Pulmonology, Groningen, Netherlands.
⁶ University of Groningen, Department of Molecular Pharmacology, Groningen Research Institute for Pharmacy, Groningen, Netherlands.
⁷ University of Groningen, University Medical Center Groningen, Department of Critical Care, Groningen, Netherlands.
⁸ University of Groningen, University Medical Center Groningen, W.J. Kolff Institute for Biomedical Engineering and Materials Science-FB41, Groningen, Netherlands.

Abstract

Environmental insults including respiratory infections, in combination with genetic predisposition, may lead to lung diseases such as chronic obstructive pulmonary disease, lung fibrosis, asthma, and acute respiratory distress syndrome. Common characteristics of these diseases are infiltration and activation of inflammatory cells and abnormal extracellular matrix (ECM) turnover, leading to tissue damage and impairments in lung function. The ECM provides three-dimensional (3D) architectural support to the lung and crucial biochemical and biophysical cues to the cells, directing cellular processes. As immune cells travel to reach any site of injury, they encounter the composition and various mechanical features of the ECM. Emerging evidence demonstrates the crucial role played by the local environment in recruiting immune cells and their function in lung diseases. Moreover, recent developments in the field have elucidated considerable differences in responses of immune cells in two-dimensional versus 3D modeling systems. Examining the effect of individual parameters of the ECM to study their effect independently and collectively in a 3D microenvironment will help in better understanding disease pathobiology. In this article, we discuss the importance of investigating cellular migration and recent advances in this field. Moreover, we summarize changes in the ECM in lung diseases and the potential impacts on infiltrating immune cell migration in these diseases. There has been compelling progress in this field that encourages further developments, such as advanced in vitro 3D modeling using native ECM-based models, patient-derived materials, and bioprinting. We conclude with an overview of these state-of-the-art methodologies, followed by a discussion on developing novel and innovative models and the practical challenges envisaged in implementing and utilizing these systems.

Keywords: extracellular matrix; in vitro models; infiltrating immune cells; lung diseases; migration; three-dimensional.

Publication types

Review