Current Diabetes Reports

, Volume 12, Issue 5, pp 471–480 | Cite as

The Role of Hyaluronan and the Extracellular Matrix in Islet Inflammation and Immune Regulation

  • Paul L. BollykyEmail author
  • Marika Bogdani
  • Jennifer B. Bollyky
  • Rebecca L. Hull
  • Thomas N. Wight
Pathogenesis of Type 1 Diabetes (AG Ziegler, Section Editor)


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.


Hyaluronan TSG-6 CD44 TLR2 TLR4 Toll-like receptors Foxp3 Regulatory T-cells TR1 Treg IL-10 TGF-β Extracellular matrix Diabetes Islets Islet inflammation Immune regulation 



This work was supported by National Institutes of Health grants DK046635 (to G.T.N.); DK080178, DK089128 and U01AI101984 (to P.L.B.); and HL018645 and a BIRT supplement AR037296 (to T.N.W.). This work was also supported by grants from the Juvenile Diabetes Research Foundation (nPOD 25-2010-648 (to T.N.W.), and The Center for Translational Research at BRI (to G.T.N.).


No potential conflicts of interest relevant to this article were reported.


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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Paul L. Bollyky
    • 1
    Email author
  • Marika Bogdani
    • 2
  • Jennifer B. Bollyky
    • 1
  • Rebecca L. Hull
    • 3
  • Thomas N. Wight
    • 1
  1. 1.Benaroya Research Institute at Virginia MasonSeattleUSA
  2. 2.Pacific Northwest Diabetes Research InstituteSeattleUSA
  3. 3.Division of Metabolism, Endocrinology, and NutritionVA Puget Sound Health Care System and University of WashingtonSeattleUSA

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