Dendritic cells and the extracellular matrix:A challenge for maintaining tolerance/homeostasis

摘要

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 inflammationinduced 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 ECMbased mimetics in regenerative medicine and other applications rely on our improved understanding of DCECM interplay in homeostasis and the challenges involved in maintaining it.