Dendritic cell functional properties in a three-dimensional tissue model of human lung mucosa
Anh Thu Nguyen Hoang1, Puran Chen, Julius Juarez
1Center for Infectious Medicine, F59, Dept. of Medicine, Karolinska Institutet, Karolinska Univ. Hospital, Huddinge, 141 86 Stockholm, Sweden.
Insights
Researchers developed a 3D human airway model to study dendritic cells (DC). This model shows that the lung tissue microenvironment regulates DC chemokine production, offering insights into immune responses.
Area of Science:
- Immunology
- Cell Biology
- Tissue Engineering
Background:
- Dendritic cells (DCs) interact closely with airway epithelium, but studying these interactions in human tissue is challenging.
- Epithelial dysfunction can trigger excessive immune cell activation, highlighting the importance of epithelial-DC communication.
- Existing models do not fully replicate the complex microenvironment of human lung mucosa.
Purpose of the Study:
- To develop a novel 3D organotypic model of human airway mucosa for studying dendritic cell (DC) interactions.
- To investigate the functional regulation of human DCs by the lung mucosal microenvironment.
- To provide a platform for dissecting DC-epithelial cell mechanisms in lung tissue.
Main Methods:
- Generation of a 3D organotypic model of human airway mucosa.
- Implantation of human dendritic cells (DCs) into the model.
- Characterization of the model's anatomical and functional features, including epithelial cell layer and protein expression.
- Imaging of live and fixed tissue sections to assess DC distribution.
- Analysis of DC chemokine production (CCL17, CCL18, CCL22) within the model.
Main Results:
- The 3D model successfully recapitulates key features of human lung mucosal tissue.
- Dendritic cells (DCs) were observed in close association with the epithelial cell layer within the model.
- The lung tissue model demonstrated regulatory effects on DC chemokine production, enhancing CCL18 and reducing CCL17/CCL22 expression.
Conclusions:
- A novel 3D organotypic model of human airway mucosa has been established, facilitating the study of dendritic cell (DC) interactions.
- This model provides a unique tool to investigate DC function within the context of the lung mucosal microenvironment.
- The findings demonstrate that the lung tissue microenvironment modulates DC chemokine profiles, offering insights into immune regulation during homeostasis and inflammation.
Abstract:
In lung tissue, dendritic cells (DC) are found in close association with the epithelial cell layer, and there is evidence of DC regulation by the epithelium; that epithelial dysfunction leads to overzealous immune cell activation. However, dissecting basic mechanisms of DC interactions with epithelial cells in human tissue is difficult. Here, we describe a method to generate a three-dimensional organotypic model of the human airway mucosa in which we have implanted human DC. The model recapitulates key anatomical and functional features of lung mucosal tissue, including a stratified epithelial cell layer, deposition of extracellular matrix proteins, and the production of tight junction and adherence junction proteins. Labeling of fixed tissue model sections and imaging of live tissue models also revealed that DC distribute in close association with the epithelial layer. As functional properties of DC may be affected by the local tissue microenvironment, this system provides a tool to study human DC function associated with lung mucosal tissue. As an example, we report that the lung tissue model regulates the capacity of DC to produce the chemokines CCL17, CCL18, and CCL22, leading to enhanced CCL18 expression and reduced CCL17 and CCL22 expression. This novel tissue model thus provides a tool well suited for a wide range of studies, including those on the regulation of DC functional properties within the local tissue microenvironment during homeostasis and inflammatory reactions.
