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Current Diabetes Reports

, 14:552 | Cite as

Extracellular Matrix Components in the Pathogenesis of Type 1 Diabetes

  • Marika Bogdani
  • Eva Korpos
  • Charmaine J. Simeonovic
  • Christopher R. Parish
  • Lydia Sorokin
  • Thomas N. WightEmail author
Pathogenesis of Type 1 Diabetes (A Pugliese, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Pathogenesis of Type 1 Diabetes

Abstract

Type 1 diabetes (T1D) results from progressive immune cell-mediated destruction of pancreatic β cells. As immune cells migrate into the islets, they pass through the extracellular matrix (ECM). This ECM is composed of different macromolecules localized to different compartments within and surrounding islets; however, the involvement of this ECM in the development of human T1D is not well understood. Here, we summarize our recent findings from human and mouse studies illustrating how specific components of the islet ECM that constitute basement membranes and interstitial matrix of the islets, and surprisingly, the intracellular composition of islet β cells themselves, are significantly altered during the pathogenesis of T1D. Our focus is on the ECM molecules laminins, collagens, heparan sulfate/heparan sulfate proteoglycans, and hyaluronan, as well as on the enzymes that degrade these ECM components. We propose that islet and lymphoid tissue ECM composition and organization are critical to promoting immune cell activation, islet invasion, and destruction of islet β cells in T1D.

Keywords

Extracellular matrix Hyaluronan Hyaladherins Laminin Heparan sulfate Cathepsins Heparanase Islet Islet infiltration Diabetes Immune regulation 

Notes

Acknowledgments

The basement membrane work was supported by the European Foundation for the Study of Diabetes/Juvenile Diabetes Research Foundation (JDRF)/Novo Nordisk A/S (BD21070), JDRF (1-2005-903), and German Research Foundation Collaborative Research Center (CRC) (1009 and SO285/9-1) (L.S.). The heparan sulfate work was supported by a National Health and Medical Research Council of Australia (NH & MRC)/JDRF Special Program Grant in Type 1 Diabetes (#418138; to C.R.P.), a NHMRC Project Grant (#1043284; to C.J.S.), and a research grant from the Roche Organ Transplantation Research Foundation (ROTRF)/JDRF (#477554991; to C.J.S.). The hyaluronan work was supported by JDRF nPOD grant 25-2010-648, and NIH/NIAID grants U01 AI101990 and U01 AI101984 (T.N.W.). This research was performed with the support of the Network for Pancreatic Organ Donors with Diabetes (nPOD), a collaborative type 1 diabetes research project sponsored by JDRF. Organ Procurement Organizations (OPO) partnering with nPOD to provide research resources are listed at http://www.jdrfnpod.org/for-partners/npod-partners/.

Compliance with Ethics Guidelines

Conflict of Interest

Marika Bogdani declares that she has no conflict of interest.

Eva Korpos declares that she has no conflict of interest.

Charmaine J. Simeonovic has received research support through a grant from The Australian National University, is currently a shareholder of Beta Therapeutics, and currently has two patents pending.

Christopher R. Parish has received research support through a grant from The Australian National University, is currently a shareholder of Beta Therapeutics, and currently has two patents pending.

Lydia Sorokin declares that she has no conflict of interest.

Thomas N. Wight declares that he has no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human subjects performed by any of the authors. Studies with animals were approved by the relevant institution’s Animal Care and Use Committee and have been previously published.

References

Papers of particular interest, published within the last 3 years, have been highlighted as: • Of importance •• Of major importance

  1. 1.••
    Hynes RO, Yamada KM. Extracellular matrix biology. Cold Spring Harbor: Cold Spring Harbor Laboratory Press; 2012. Excellent up-to-date coverage of different ECM components.Google Scholar
  2. 2.••
    Karamanos N. Extracellular matrix: pathobiology and signaling. Berlin/Boston: Walter de Gruyter; 2012. Outstanding collection of chapters covering information on how different components of ECM impact cellular signaling and cell phenotype.Google Scholar
  3. 3.
    Mecham RP, editor. The extracellular matrix: an overview. Biology of the extracellular matrix. Berlin: Springer-Verlag; 2011.Google Scholar
  4. 4.
    Hay ED. Cell biology of extracellular matrix. New York: Plenum Press; 1991.CrossRefGoogle Scholar
  5. 5.
    Sorokin L. The impact of the extracellular matrix on inflammation. Nat Rev Immunol. 2010;10:712–23. doi: 10.1038/nri2852.PubMedCrossRefGoogle Scholar
  6. 6.
    Pugliese A, Yang M, Kusmarteva I, Heiple T, Vendrame F, Wasserfall C, et al. The Juvenile Diabetes Research Foundation Network for Pancreatic Organ Donors with Diabetes (nPOD) Program: goals, operational model and emerging findings. Pediatr Diabetes. 2014;15:1–9. doi: 10.1111/pedi.12097.PubMedCrossRefGoogle Scholar
  7. 7.
    Jiang FX, Harrison LC. Extracellular signals and pancreatic beta-cell development: a brief review. Mol Med. 2002;8:763–70.PubMedCentralPubMedGoogle Scholar
  8. 8.••
    Reinert RB, Cai Q, Hong JY, Plank JL, Aamodt K, Prasad N, et al. Vascular endothelial growth factor coordinates islet innervation via vascular scaffolding. Development. 2014;141:1480–91. doi: 10.1242/dev.098657. This study shows the interconnection between the vascular and neuronal system in pancreatic islet development.PubMedCrossRefGoogle Scholar
  9. 9.••
    Nikolova G, Jabs N, Konstantinova I, Domogatskaya A, Tryggvason K, Sorokin L, et al. The vascular basement membrane: a niche for insulin gene expression and beta cell proliferation. Dev Cell. 2006;10:397–405. doi: 10.1016/j.devcel.2006.01.015. This study shows how laminins can impact on islet development and insulin production, an area with enormous potential for improved islet transfer.PubMedCrossRefGoogle Scholar
  10. 10.
    Virtanen I, Banerjee M, Palgi J, Korsgren O, Lukinius A, Thornell LE, et al. Blood vessels of human islets of Langerhans are surrounded by a double basement membrane. Diabetologia. 2008;51:1181–91. doi: 10.1007/s00125-008-0997-9.PubMedCrossRefGoogle Scholar
  11. 11.
    Otonkoski T, Banerjee M, Korsgren O, Thornell LE, Virtanen I. Unique basement membrane structure of human pancreatic islets: implications for beta-cell growth and differentiation. Diabetes Obes Metab. 2008;10 Suppl 4:119–27. doi: 10.1111/j.1463-1326.2008.00955.x.PubMedCrossRefGoogle Scholar
  12. 12.
    Pavin EJ, Pinto GA, Zollner RL, Vassallo J. Immunohistochemical study of the pancreatic basement membrane in non obese diabetic mice (NOD) with spontaneous autoimmune insulitis. J Submicrosc Cytol Pathol. 2003;35:25–7.PubMedGoogle Scholar
  13. 13.
    Irving-Rodgers HF, Ziolkowski AF, Parish CR, Sado Y, Ninomiya Y, Simeonovic CJ, et al. Molecular composition of the peri-islet basement membrane in NOD mice: a barrier against destructive insulitis. Diabetologia. 2008;51:1680–8. doi: 10.1007/s00125-008-1085-x.PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.••
    Ziolkowski AF, Popp SK, Freeman C, Parish CR, Simeonovic CJ. Heparan sulfate and heparanase play key roles in mouse beta cell survival and autoimmune diabetes. J Clin Invest. 2012;122:132–41. doi: 10.1172/JCI46177. Hallmark study identifies heparan sulfate (HS) to be critical for islet beta cell survival and HS-degrading heparanase as a novel mechanism of beta cell death in T1D.PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.••
    Korpos E, Kadri N, Kappelhoff R, Wegner J, Overall CM, Weber E, et al. The peri-islet basement membrane, a barrier to infiltrating leukocytes in type 1 diabetes in mouse and human. Diabetes. 2013;62:531–42. doi: 10.2337/db12-0432. This work shows that the peri-islet basement membrane is a barrier in front of pancreatic islet infiltrating leukocyte not only in NOD mice but also in human type 1 diabetic pancreases.PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Tanzer ML. Current concepts of extracellular matrix. J Orthop Sci. 2006;11:326–31. doi: 10.1007/s00776-006-1012-2.PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.••
    Hynes RO. The extracellular matrix: not just pretty fibrils. Science. 2009;326:1216–9. doi: 10.1126/science.1176009. An excellent overview of what the ECM is and how it can impact cellular behavior.PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Frantz C, Stewart KM, Weaver VM. The extracellular matrix at a glance. J Cell Sci. 2010;123:4195–200. doi: 10.1242/jcs.023820.PubMedCentralPubMedCrossRefGoogle Scholar
  19. 19.
    Robert L, Robert AM, Renard G. Biological effects of hyaluronan in connective tissues, eye, skin, venous wall. Role in aging Pathol Biol (Paris). 2010;58:187–98. doi: 10.1016/j.patbio.2009.09.010.CrossRefGoogle Scholar
  20. 20.••
    Bogdani M, Johnson PY, Potter-Perigo S, Nagy N, Day AJ, Bollyky PL, et al. Hyaluronan and hyaluronan binding proteins accumulate in both human type 1 diabetic islets and lymphoid tissues and associate with inflammatory cells in insulitis. Diabetes. 2014;63:2727–43. doi: 10.2337/db13-1658. A thorough investigation of the involvement of hyaluronan and associated molecules in the pathogenesis of T1D.
  21. 21.
    Behrens DT, Villone D, Koch M, Brunner G, Sorokin L, Robenek H, et al. The epidermal basement membrane is a composite of separate laminin- or collagen IV-containing networks connected by aggregated perlecan, but not by nidogens. J Biol Chem. 2012;287:18700–9. doi: 10.1074/jbc.M111.336073.PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Fox JW, Mayer U, Nischt R, Aumailley M, Reinhardt D, Wiedemann H, et al. Recombinant nidogen consists of three globular domains and mediates binding of laminin to collagen type IV. EMBO J. 1991;10:3137–46.PubMedCentralPubMedGoogle Scholar
  23. 23.
    Mayer U, Kohfeldt E, Timpl R. Structural and genetic analysis of laminin-nidogen interaction. Ann NY Acad Sci. 1998;857:130–42.PubMedCrossRefGoogle Scholar
  24. 24.
    Mayer U, Mann K, Timpl R, Murphy G. Sites of nidogen cleavage by proteases involved in tissue homeostasis and remodelling. Eur J Biochem. 1993;217:877–84.PubMedCrossRefGoogle Scholar
  25. 25.
    Aumailley M, Battaglia C, Mayer U, Reinhardt D, Nischt R, Timpl R, et al. Nidogen mediates the formation of ternary complexes of basement membrane components. Kidney Int. 1993;43:7–12.PubMedCrossRefGoogle Scholar
  26. 26.
    Poschl E, Schlotzer-Schrehardt U, Brachvogel B, Saito K, Ninomiya Y, Mayer U. Collagen IV is essential for basement membrane stability but dispensable for initiation of its assembly during early development. Development. 2004;131:1619–28. doi: 10.1242/dev.01037.PubMedCrossRefGoogle Scholar
  27. 27.
    Durbeej M. Laminins Cell Tissue Res. 2010;339:259–68. doi: 10.1007/s00441-009-0838-2.CrossRefGoogle Scholar
  28. 28.
    Parish CR. The role of heparan sulphate in inflammation. Nat Rev Immunol. 2006;6:633–43.PubMedCrossRefGoogle Scholar
  29. 29.
    Jiang FX, Naselli G, Harrison LC. Distinct distribution of laminin and its integrin receptors in the pancreas. J Histochem Cytochem. 2002;50:1625–32.PubMedCrossRefGoogle Scholar
  30. 30.
    Banerjee M, Virtanen I, Palgi J, Korsgren O, Otonkoski T. Proliferation and plasticity of human beta cells on physiologically occurring laminin isoforms. Mol Cell Endocrinol. 2012;355:78–86. doi: 10.1016/j.mce.2012.01.020.PubMedCrossRefGoogle Scholar
  31. 31.
    Van Deijnen JH, Van Suylichem PT, Wolters GH, Van Schilfgaarde R. Distribution of collagens type I, type III and type V in the pancreas of rat, dog, pig and man. Cell Tissue Res. 1994;277:115–21.PubMedCrossRefGoogle Scholar
  32. 32.
    Burns AR, Smith CW, Walker DC. Unique structural features that influence neutrophil emigration into the lung. Physiol Rev. 2003;83:309–36. doi: 10.1152/physrev.00023.2002.PubMedGoogle Scholar
  33. 33.
    Ley K, Laudanna C, Cybulsky MI, Nourshargh S. Getting to the site of inflammation: the leukocyte adhesion cascade updated. Nat Rev Immunol. 2007;7:678–89. doi: 10.1038/nri2156.PubMedCrossRefGoogle Scholar
  34. 34.
    Brunicardi FC, Stagner J, Bonner-Weir S, Wayland H, Kleinman R, Livingston E, et al. Microcirculation of the islets of Langerhans. Long Beach Veterans Administration Regional Medical Education Center Symposium. Diabetes. 1996;45:385–92.PubMedCrossRefGoogle Scholar
  35. 35.
    Sixt M, Engelhardt B, Pausch F, Hallmann R, Wendler O, Sorokin LM. Endothelial cell laminin isoforms, laminins 8 and 10, play decisive roles in T cell recruitment across the blood–brain barrier in experimental autoimmune encephalomyelitis. J Cell Biol. 2001;153:933–46.PubMedCentralPubMedCrossRefGoogle Scholar
  36. 36.
    Wang S, Voisin MB, Larbi KY, Dangerfield J, Scheiermann C, Tran M, et al. Venular basement membranes contain specific matrix protein low expression regions that act as exit points for emigrating neutrophils. J Exp Med. 2006;203:1519–32.PubMedCentralPubMedCrossRefGoogle Scholar
  37. 37.
    Wu C, Ivars F, Anderson P, Hallmann R, Vestweber D, Nilsson P, et al. Endothelial basement membrane laminin alpha5 selectively inhibits T lymphocyte extravasation into the brain. Nat Med. 2009;15:519–27. doi: 10.1038/nm.1957.PubMedCrossRefGoogle Scholar
  38. 38.
    Kenne E, Soehnlein O, Genove G, Rotzius P, Eriksson EE, Lindbom L. Immune cell recruitment to inflammatory loci is impaired in mice deficient in basement membrane protein laminin alpha4. J Leukoc Biol. 2010;88:523–8. doi: 10.1189/jlb.0110043.PubMedGoogle Scholar
  39. 39.
    Kappelhoff R, Overall C. The CLIP-CHIP oligonucleotide microarray: dedicated array for analysis of all protease, nonproteolytic homolog, and inhibitor gene transcripts in human and mouse. Curr Protoc Protein Sci 2007. p. Unit 21 19.Google Scholar
  40. 40.
    Gocheva V, Wang HW, Gadea BB, Shree T, Hunter KE, Garfall AL, et al. IL-4 induces cathepsin protease activity in tumor-associated macrophages to promote cancer growth and invasion. Genes Dev. 2010;24:241–55. doi: 10.1101/gad.1874010.PubMedCentralPubMedCrossRefGoogle Scholar
  41. 41.
    Wang B, Sun J, Kitamoto S, Yang M, Grubb A, Chapman HA, et al. Cathepsin S controls angiogenesis and tumor growth via matrix-derived angiogenic factors. J Biol Chem. 2006;281:6020–9. doi: 10.1074/jbc.M509134200.PubMedCrossRefGoogle Scholar
  42. 42.
    Abdul-Hussien H, Soekhoe RG, Weber E, von der Thusen JH, Kleemann R, Mulder A, et al. Collagen degradation in the abdominal aneurysm: a conspiracy of matrix metalloproteinase and cysteine collagenases. Am J Pathol. 2007;170:809–17. doi: 10.2353/ajpath.2007.060522.PubMedCentralPubMedCrossRefGoogle Scholar
  43. 43.
    Chang SH, Kanasaki K, Gocheva V, Blum G, Harper J, Moses MA, et al. VEGF-A induces angiogenesis by perturbing the cathepsin-cysteine protease inhibitor balance in venules, causing basement membrane degradation and mother vessel formation. Cancer Res. 2009;69:4537–44. doi: 10.1158/0008-5472.PubMedCentralPubMedCrossRefGoogle Scholar
  44. 44.
    Morrison CJ, Butler GS, Rodriguez D, Overall CM. Matrix metalloproteinase proteomics: substrates, targets, and therapy. Curr Opin Cell Biol. 2009;21:645–53. doi: 10.1016/j.ceb.2009.06.006.PubMedCrossRefGoogle Scholar
  45. 45.••
    Dufour A, Overall CM. Missing the target: matrix metalloproteinase antitargets in inflammation and cancer. Trends Pharmacol Sci. 2013;34:233–42. doi: 10.1016/j.tips.2013.02.004. This review summarizes the novel substrates of matrix metalloproteinases in inflammation and cancer.PubMedCrossRefGoogle Scholar
  46. 46.
    Weathington NM, van Houwelingen AH, Noerager BD, Jackson PL, Kraneveld AD, Galin FS, et al. A novel peptide CXCR ligand derived from extracellular matrix degradation during airway inflammation. Nat Med. 2006;12:317–23. doi: 10.1038/nm1361.PubMedCrossRefGoogle Scholar
  47. 47.
    Ricard-Blum S, Salza R. Matricryptins and matrikines: biologically active fragments of the extracellular matrix. Exp Dermatol. 2014. doi: 10.1111/exd.12435.PubMedGoogle Scholar
  48. 48.
    Bernfield M, Gotte M, Park PW, Reizes O, Fitzgerald ML, Lincecum J, et al. Functions of cell surface heparan sulfate proteoglycans. Annu Rev Biochem. 1999;68:729–77. doi: 10.1146/annurev.biochem.68.1.729.
  49. 49.
    Esko JD, Selleck SB. Order out of chaos: assembly of ligand binding sites in heparan sulfate. Annu Rev Biochem. 2002;71:435–71. doi: 10.1146/annurev.biochem.71.110601.135458.PubMedCrossRefGoogle Scholar
  50. 50.
    Lindahl U, Kjellen L. Pathophysiology of heparan sulphate: many diseases, few drugs. J Intern Med. 2013;273:555–71. doi: 10.1111/joim.12061.PubMedCrossRefGoogle Scholar
  51. 51.
    Sarrazin S, Lamanna WC, Esko JD. Heparan sulfate proteoglycans. Cold Spring Harb Perspect Biol. 2011;3. doi: 10.1101/cshperspect.a004952.
  52. 52.
    Kreuger J, Kjellen L. Heparan sulfate biosynthesis: regulation and variability. J Histochem Cytochem. 2012;60:898–907. doi: 10.1369/0022155412464972.PubMedCentralPubMedCrossRefGoogle Scholar
  53. 53.
    Casu B, Naggi A, Torri G. Heparin-derived heparan sulfate mimics that modulate inflammation and cancer. Matrix Biol 2010;29:442–52. doi: 10.1016/j.matbio.2010.04.003.
  54. 54.
    Hohenester E, Yurchenco PD. Laminins in basement membrane assembly. Cell Adh Migr. 2013;7:56–63. doi: 10.4161/cam.21831.PubMedCentralPubMedCrossRefGoogle Scholar
  55. 55.
    Dilts SM, Lafferty KJ. Autoimmune diabetes: the involvement of benign and malignant autoimmunity. J Autoimmun. 1999;12:229–32. doi: 10.1006/jaut.1999.0284.PubMedCrossRefGoogle Scholar
  56. 56.
    Solomon M, Sarvetnick N. The pathogenesis of diabetes in the NOD mouse. Adv Immunol. 2004;84:239–64. doi: 10.1016/S0065-2776(04)84007-0.PubMedCrossRefGoogle Scholar
  57. 57.
    Tsiapali E, Whaley S, Kalbfleisch J, Ensley HE, Browder IW, Williams DL. Glucans exhibit weak antioxidant activity, but stimulate macrophage free radical activity. Free Radic Biol Med. 2001;30:393–402. doi: 10.1016/S0891-5849(00)00485-8.
  58. 58.
    Takahashi I, Noguchi N, Nata K, Yamada S, Kaneiwa T, Mizumoto S, et al. Important role of heparan sulfate in postnatal islet growth and insulin secretion. Biochem Biophys Res Commun. 2009;383:113–8. doi: 10.1016/j.bbrc.2009.03.140.PubMedCrossRefGoogle Scholar
  59. 59.
    Vlodavsky I, Friedmann Y. Molecular properties and involvement of heparanase in cancer metastasis and angiogenesis. J Clin Invest. 2001;108:341–7. doi: 10.1172/JCI13662.PubMedCentralPubMedCrossRefGoogle Scholar
  60. 60.
    Couzin-Frankel J. Clinical studies. Trying to reset the clock on type 1 diabetes. Science. 2011;333:819–21. doi: 10.1126/science.333.6044.819.
  61. 61.
    DeWeerdt S. Immunomodulators: cell savers. Nature. 2012;485:S4–5.PubMedCrossRefGoogle Scholar
  62. 62.
    Weissmann B, Meyer K. The structure of hyalobiuronic acid and of hyaluronic acid from umbilical cord. J Am Chem Soc. 1954;76:1753–7.CrossRefGoogle Scholar
  63. 63.
    Laurent TC, Laurent UB, Fraser JR. The structure and function of hyaluronan: an overview. Immunol Cell Biol. 1996;74:A1–7. doi: 10.1038/icb.1996.32.PubMedCrossRefGoogle Scholar
  64. 64.
    Toole BP. Hyaluronan: from extracellular glue to pericellular cue. Nat Rev Cancer. 2004;4:528–39.PubMedCrossRefGoogle Scholar
  65. 65.
    Volpi N, Schiller J, Stern R, Soltes L. Role, metabolism, chemical modifications and applications of hyaluronan. Curr Med Chem. 2009;16:1718–45.PubMedCrossRefGoogle Scholar
  66. 66.
    Day AJ, Prestwich GD. Hyaluronan-binding proteins: tying up the giant. J Biol Chem. 2002;277:4585–8.PubMedCrossRefGoogle Scholar
  67. 67.
    Jiang D, Liang J, Noble PW. Hyaluronan as an immune regulator in human diseases. Physiol Rev. 2011;91:221–64. doi: 10.1152/physrev.00052.2009.PubMedCentralPubMedCrossRefGoogle Scholar
  68. 68.••
    Csoka AB, Stern R. Hypotheses on the evolution of hyaluronan: a highly ironic acid. Glycobiology. 2013;23:398–411. doi: 10.1093/glycob/cws218. Outstanding review of functional aspects of hyaluronan biology—thought provoking.PubMedCentralPubMedCrossRefGoogle Scholar
  69. 69.
    Tian X, Azpurua J, Hine C, Vaidya A, Myakishev-Rempel M, Ablaeva J, et al. High-molecular-mass hyaluronan mediates the cancer resistance of the naked mole rat. Nature. 2013;499:346–9. doi: 10.1038/nature12234.PubMedCentralPubMedCrossRefGoogle Scholar
  70. 70.
    Stern R, Asari AA, Sugahara KN. Hyaluronan fragments: an information-rich system. Eur J Cell Biol. 2006;85:699–715.PubMedCrossRefGoogle Scholar
  71. 71.
    Fraser JR, Laurent TC, Laurent UB. Hyaluronan: its nature, distribution, functions and turnover. J Intern Med. 1997;242:27–33.PubMedCrossRefGoogle Scholar
  72. 72.
    Day AJ, de la Motte CA. Hyaluronan cross-linking: a protective mechanism in inflammation? Trends Immunol. 2005;26:637–43.PubMedCrossRefGoogle Scholar
  73. 73.••
    Bollyky PL, Bogdani M, Bollyky JB, Hull RL, Wight TN. The role of hyaluronan and the extracellular matrix in islet inflammation and immune regulation. Curr Diab Rep. 2012;12:471–80. doi: 10.1007/s11892-012-0297-0. An excellent review of how hyaluronan regulates innate and adaptive immunity.PubMedCentralPubMedCrossRefGoogle Scholar
  74. 74.
    de la Motte CA. Hyaluronan in intestinal homeostasis and inflammation: implications for fibrosis. Am J Physiol Gastrointest Liver Physiol. 2011;301:G945–9. doi: 10.1152/ajpgi.00063.2011.PubMedCentralPubMedCrossRefGoogle Scholar
  75. 75.
    Lesley J, Gal I, Mahoney DJ, Cordell MR, Rugg MS, Hyman R, et al. TSG-6 modulates the interaction between hyaluronan and cell surface CD44. J Biol Chem. 2004;279:25745–54.PubMedCrossRefGoogle Scholar
  76. 76.
    Potter-Perigo S, Johnson PY, Evanko SP, Chan CK, Braun KR, Wilkinson TS, et al. Polyinosine-polycytidylic acid stimulates versican accumulation in the extracellular matrix promoting monocyte adhesion. Am J Respir Cell Mol Biol. 2010;43:109–20. doi: 10.1165/rcmb.2009-0081OC.PubMedCentralPubMedCrossRefGoogle Scholar
  77. 77.••
    Evanko SP, Potter-Perigo S, Bollyky PL, Nepom GT, Wight TN. Hyaluronan and versican in the control of human T-lymphocyte adhesion and migration. Matrix Biol. 2012;31:90–100. doi: 10.1016/j.matbio.2011.10.004. A nice demonstration of how these components affect T-cell phenotype.PubMedCentralPubMedCrossRefGoogle Scholar
  78. 78.••
    Baranova NS, Foulcer SJ, Briggs DC, Tilakaratna V, Enghild JJ, Milner CM, et al. Inter-α-inhibitor impairs TSG-6 induced hyaluronan cross-linking. J Biol Chem. 2013;288:29642–53. doi: 10.1074/jbc.M113.477422. Insightful study demonstrating key molecules in the generation of high molecular complexes of hyaluronan.PubMedCentralPubMedCrossRefGoogle Scholar
  79. 79.
    Wang A, de la Motte C, Lauer M, Hascall V. Hyaluronan matrices in pathobiological processes. FEBS J. 2011;278:1412–8. doi: 10.1111/j.1742-4658.2011.08069.x.PubMedCrossRefGoogle Scholar
  80. 80.
    Baranova NS, Nileback E, Haller FM, Briggs DC, Svedhem S, Day AJ, et al. The inflammation-associated protein TSG-6 cross-links hyaluronan via hyaluronan-induced TSG-6 oligomers. J Biol Chem. 2011;286:25675–86. doi: 10.1074/jbc.M111.247395.PubMedCentralPubMedCrossRefGoogle Scholar
  81. 81.
    Stern R, Jedrzejas MJ. Hyaluronidases: their genomics, structures, and mechanisms of action. Chem Rev. 2006;106:818–39. doi: 10.1021/cr050247k.PubMedCentralPubMedCrossRefGoogle Scholar
  82. 82.
    Teder P, Vandivier RW, Jiang D, Liang J, Cohn L, Pure E, et al. Resolution of lung inflammation by CD44. Science. 2002;296:155–8.PubMedCrossRefGoogle Scholar
  83. 83.
    Powell JD, Horton MR. Threat matrix: low-molecular-weight hyaluronan (HA) as a danger signal. Immunol Res. 2005;31:207–18.PubMedCrossRefGoogle Scholar
  84. 84.
    Atkinson MA, Gianani R. The pancreas in human type 1 diabetes: providing new answers to age-old questions. Curr Opin Endocrinol Diabetes Obes. 2009;16:279–85. doi: 10.1097/MED.0b013e32832e06ba.PubMedCrossRefGoogle Scholar
  85. 85.
    Eizirik DL, Colli ML, Ortis F. The role of inflammation in insulitis and beta-cell loss in type 1 diabetes. Nat Rev Endocrinol. 2009;5:219–26. doi: 10.1038/nrendo.2009.21.PubMedCrossRefGoogle Scholar
  86. 86.
    Galandrini R, Galluzzo E, Albi N, Grossi CE, Velardi A. Hyaluronate is costimulatory for human T cell effector functions and binds to CD44 on activated T cells. J Immunol. 1994;153:21–31.PubMedGoogle Scholar
  87. 87.
    Mummert ME, Mohamadzadeh M, Mummert DI, Mizumoto N, Takashima A. Development of a peptide inhibitor of hyaluronan-mediated leukocyte trafficking. J Exp Med. 2000;192:769–79.PubMedCentralPubMedCrossRefGoogle Scholar
  88. 88.
    Mummert ME, Mummert D, Edelbaum D, Hui F, Matsue H, Takashima A. Synthesis and surface expression of hyaluronan by dendritic cells and its potential role in antigen presentation. J Immunol. 2002;169:4322–31.PubMedCrossRefGoogle Scholar
  89. 89.
    Mummert ME. Immunologic roles of hyaluronan. Immunol Res. 2005;31:189–206.PubMedCrossRefGoogle Scholar
  90. 90.
    Bollyky P, Evanko S, Wu R, Potter-Perigo S, Long S, Kinsella B, et al. TH1 cytokines promote hyaluronan production by antigen presenting cells and accumulation at the immune synapse. Cell Mol Immunol. 2010;7:211–20. doi: 10.1038/cmi.2010.9.PubMedCentralPubMedCrossRefGoogle Scholar
  91. 91.
    Weiss L, Slavin S, Reich S, Cohen P, Shuster S, Stern R, et al. Induction of resistance to diabetes in non-obese diabetic mice by targeting CD44 with a specific monoclonal antibody. Proc Natl Acad Sci U S A. 2000;97:285–90.PubMedCentralPubMedCrossRefGoogle Scholar
  92. 92.••
    Kota DJ, Wiggins LL, Yoon N, Lee RH. TSG-6 produced by hMSCs delays the onset of autoimmune diabetes by suppressing Th1 development and enhancing tolerogenicity. Diabetes. 2013;62:2048–58. doi: 10.2337/db12-0931. Interesting study implicating a hyaluronan binding protein as a possible therapeutic target to treat T1D.PubMedCentralPubMedCrossRefGoogle Scholar
  93. 93.
    Willcox A, Richardson SJ, Bone AJ, Foulis AK, Morgan NG. Analysis of islet inflammation in human type 1 diabetes. Clin Exp Immunol. 2009;155:173–81. doi: 10.1111/j.1365-2249.2008.03860.x.PubMedCentralPubMedCrossRefGoogle Scholar
  94. 94.
    Coppieters KT, Dotta F, Amirian N, Campbell PD, Kay TW, Atkinson MA, et al. Demonstration of islet-autoreactive CD8 T cells in insulitic lesions from recent onset and long-term type 1 diabetes patients. J Exp Med. 2012;209:51–60. doi: 10.1084/jem.20111187.PubMedCentralPubMedCrossRefGoogle Scholar
  95. 95.
    Bajenoff M, Egen JG, Koo LY, Laugier JP, Brau F, Glaichenhaus N, et al. Stromal cell networks regulate lymphocyte entry, migration, and territoriality in lymph nodes. Immunity. 2006;25:989–1001. doi: 10.1016/j.immuni.2006.10.011.PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Marika Bogdani
    • 1
  • Eva Korpos
    • 2
  • Charmaine J. Simeonovic
    • 3
  • Christopher R. Parish
    • 4
  • Lydia Sorokin
    • 2
  • Thomas N. Wight
    • 1
    Email author
  1. 1.Matrix Biology ProgramBenaroya Research InstituteSeattleUSA
  2. 2.Institute of Physiological Chemistry and Pathobiochemistry, Cells-in-Motion Cluster of Excellence (EXC 1003 – CiM)University of MünsterMünsterGermany
  3. 3.Diabetes/Transplantation Immunobiology Laboratory, The John Curtin School of Medical ResearchThe Australian National UniversityCanberraAustralia
  4. 4.Cancer and Vascular Biology Group, Department of Immunology, The John Curtin School of Medical ResearchThe Australian National UniversityCanberraAustralia

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