The role of hyaluronan and the extracellular matrix in islet inflammation and immune regulation.
Type 1 diabetes (T1D) is a disease that in most individuals results from autoimmune attack of a single tissue type, the pancreatic islet. A fundamental, unanswered question in T1D pathogenesis is how the islet tissue environment influences immune regulation. This crosstalk is likely to be communicated through the extracellular matrix (ECM). Here, we review what is known about the ECM in insulitis and examine how the tissue environment is synchronized with immune regulation. In particular, we focus on the role of hyaluronan (HA) and its interactions with Foxp3+ regulatory T-cells (Treg). We propose that HA is a "keystone molecule" in the inflammatory milieu and that HA, together with its associated binding proteins and receptors, is an appropriate point of entry for investigations into how ECM influences immune regulation in the islet.
Benaroya Research Institute at Virginia Mason, Seattle, WA 98101, USA. pbollyky@benaroyaresearch.org
Paul L
PL
Bollyky
Marika
M
Bogdani
Jennifer B
JB
Bollyky
Rebecca L
RL
Hull
Thomas N
TN
Wight
D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D006820:Hyaluronic Acid / Q000378:metabolism*; D007515:Islets of Langerhans / Q000378:metabolism*; D008954:Models, Biological
D018960:Hyaluronan Receptors; D006820:Hyaluronic Acid