Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Immunol. Nov 27, 2015; 5(3): 113-130
Published online Nov 27, 2015. doi: 10.5411/wji.v5.i3.113
Dendritic cells and the extracellular matrix: A challenge for maintaining tolerance/homeostasis
Sucharita P Shankar, May Griffith, John V Forrester, Lucia Kuffová
Sucharita P Shankar, John V Forrester, Lucia Kuffová, Section of Immunology, Inflammation and Infection, Division of Applied Medicine, School of Medicine and Dentistry, University of Aberdeen, Institute of Medical Sciences, Scotland AB25 2ZD, United Kingdom
May Griffith, Integrative Regenerative Medicine Centre, Department of Clinical and Experimental Medicine, Cell Biology Bldg. Level 10, Linköping University, S-58185 Linköping, Sweden
May Griffith, Department of Ophthalmology, Maisonneuve-Rosemont Hospital, Montreal, QC H1T 2M4, Canada
Author contributions: Shankar SP performed the experiments, conducted the literature review and writing of the manuscript; Griffith M performed certain experiments and provided intellectual input; Forrester JV provided intellectual input, critical revision and approval of the final version; Kuffová L performed certain experiments and contributed to writing the manuscript.
Supported by The Royal College of Surgeons of Edinburgh.
Conflict-of-interest statement: Authors declare no conflict of interests for this article.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Dr. Lucia Kuffová, MD, PhD, Section of Immunology, Inflammation and Infection, Division of Applied Medicine, School of Medicine and Dentistry, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen, Scotland AB25 2ZD, United Kingdom.
Telephone: +44-1224-437505 Fax: +44-1224-437506
Received: July 23, 2015
Peer-review started: July 27, 2015
First decision: August 25, 2015
Revised: September 18, 2015
Accepted: November 10, 2015
Article in press: November 11, 2015
Published online: November 27, 2015

The importance of the extracellular matrix (ECM) in contributing to structural, mechanical, functional and tissue-specific features in the body is well appreciated. While the ECM was previously considered to be a passive bystander, it is now evident that it plays active, dynamic and flexible roles in shaping cell survival, differentiation, migration and death to varying extents depending on the specific site in the body. Dendritic cells (DCs) are recognized as potent antigen presenting cells present in many tissues and in blood, continuously scrutinizing the microenvironment for antigens and mounting local and systemic host responses against harmful agents. DCs also play pivotal roles in maintaining homeostasis to harmless self-antigens, critical for preventing autoimmunity. What is less understood are the complex interactions between DCs and the ECM in maintaining this balance between steady-state tissue residence and DC activation during inflammation. DCs are finely tuned to inflammation-induced variations in fragment length, accessible epitopes and post-translational modifications of individual ECM components and correspondingly interpret these changes appropriately by adjusting their profiles of cognate binding receptors and downstream immune activation. The successful design and composition of novel ECM-based mimetics in regenerative medicine and other applications rely on our improved understanding of DC-ECM interplay in homeostasis and the challenges involved in maintaining it.

Keywords: Dendritic cells, Extracellular matrix, Tolerance, Biomaterials, Homeostasis, Regenerative medicine, Biointeractive implants

Core tip: The extracellular matrix (ECM) provides an essential framework for tissues in the body as well as actively orchestrates diverse cellular functions. Professional antigen presenting cells namely dendritic cells (DCs) are uniquely positioned to distinguish between self and non-self and accordingly regulate systemic immunity or tolerance. DCs and the ECM participate in finely-tuned, dynamic exchanges that ultimately impact the equilibrium between steady-state DC tissue residence or DC-instigated inflammation. To design biointeractive, ECM-inspired implants for regenerative medicine applications that retain functionality and undergo successful integration long-term, it is critical to understand the challenges involved in maintaining DC-ECM immune homeostasis under normal conditions.