Published online Nov 27, 2015. doi: 10.5411/wji.v5.i3.113
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.
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.