Culture of dendritic cells in fibronectin-collagen hydrogel to reconstruct communication of ECM to the adaptive immune system

Dendritic cells (DCs) are professional antigen-presenting cells that connect innate and adaptive immunity. In lymphoid tissues, DCs interact with the surrounding extracellular matrix (ECM) proteins. Fibronectin (FN) organizes the connective tissue stroma of the secondary lymphoid tissues, creating immune microenvironments. FN, but not laminin and collagen, inhibited activation of DCs stimulated by lipopolysaccharide (LPS) and other stimulants. FN- and LPS-treated DCs failed to induce proliferation of T cells. FN was detected in splenic tissue, and its staining decreased in the spleen 6 h after LPS injection in mice and recovered by 12 h. FN degradation and DC activation occurred in neutrophil-depleted mice. DCs cultured in FN-collagen gel were not activated by adding LPS alone. To reconstruct a lymphoid tissue inflammatory model, DCs were cultured in FN-collagen gel, neutrophils and macrophages were cultured on the gel surface, and LPS was added to the culture solution. DCs in FN-collagen with cocultured neutrophils and macrophages were activated by LPS addition. FN was degraded by proteases and MMPs secreted from LPS-stimulated macrophages and neutrophils. These findings explain how inflammatory cells communicate ECM degradation to the adaptive immune system.

Dr. Kwak is a professor at the Department of Pharmacology, Ajou University School of Medicine, South Korea. He is currently Director of the Immune-Network Pioneer Research Center at Ajou University Medical Center. He became a vice-president of the Korean Society of Biochemistry and Molecular Biology in 2015 and has been a Doctor Honoris Causa in the Russian Academy of Sciences since 2012. He earned his doctorate in Medical Biochemistry, focusing on neutrophil activation and signal transduction pathways, from Pusan National University, Korea, in 1991. After studying neutrophil activation at Emory University as a postdoctoral researcher, he directed his research to dendritic cell analysis. Current research topics in his laboratory include primary dendritic cell culture and regulation, and the development of primary cell culture-based organoids. He founded Nanofaenetech, Inc., and became CEO.