Abstract
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.
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.
| Original language | English |
|---|---|
| Pages (from-to) | 113-130 |
| Number of pages | 18 |
| Journal | World Journal of Immunology |
| Volume | 5 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 27 Nov 2015 |
Bibliographical note
Supported by The Royal College of Surgeons of Edinburgh.ACKNOWLEDGMENTS
We would like to thank the Microscopy Core Facility and the Medical Research Facility at the University of Aberdeen for technical assistance. All experiments on animals were performed according to the guidelines described in the Association for Research in Vision and Ophthalmology Statement for the Use of Animals in Vision and Ophthalmic Research and Animal License Act (United Kingdom).
Keywords
- dendritic cells
- extracellular matrix
- tolerance
- homeostasis
- biomaterials
- regenerative medicine
- biointeractive implants