Tissue transglutaminase treatment leads to concentration-dependent changes in dendritic cell phenotype - implications for the role of transglutaminase in coeliac disease

BMC Immunology

Amir M Ghaemmaghami¹  David YS Chau¹  William J Dalleywater¹ 

[1] Allergy and Tissue Modelling Research Group, School of Molecular Medical Sciences, Queen's Medical Centre, The University of Nottingham, A Floor, West Block, Nottingham, NG7 2UH, UK

关键词: Transglutaminase;    Tissue engineering;    Gliadin;    Immune response;    Dendritic cells;    Coeliac disease;   

Others  :  1077923
DOI  :  10.1186/1471-2172-13-20

 received in 2011-12-15, accepted in 2012-04-16,  发布年份 2012

【 摘 要 】

Dendritic cells (DCs) are part of the innate immune system with a key role in initiating and modulating T cell mediated immune responses. Coeliac disease is caused by inappropriate activation of such a response leading to small intestinal inflammation when gluten is ingested. Tissue transglutaminase, an extracellular matrix (ECM) protein, has an established role in coeliac disease; however, little work to date has examined its impact on DCs. The aim of this study was to investigate the effect of small intestinal ECM proteins, fibronectin (FN) and tissue transglutaminase 2 (TG-2), on human DCs by including these proteins in DC cultures.

The study used flow cytometry and scanning electron microscopy to determine the effect of FN and TG-2 on phenotype, endocytic ability and and morphology of DCs. Furthermore, DCs treated with FN and TG-2 were cultured with T cells and subsequent T cell proliferation and cytokine profile was determined.

The data indicate that transglutaminase affected DCs in a concentration-dependent manner. High concentrations were associated with a more mature phenotype and increased ability to stimulate T cells, while lower concentrations led to maintenance of an immature phenotype.

These data provide support for an additional role for transglutaminase in coeliac disease and demonstrate the potential of in vitro modelling of coeliac disease pathogenesis.

【 授权许可】

   
2012 Dalleywater et al; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

【 参考文献 】

• [1]García-Nieto S, Johal RK, Shakesheff KM, Emara M, Royer PJ, Chau DY, Shakib F, Ghaemmaghami AM: Laminin and fibronectin treatment leads to generation of dendritic cells with superior endocytic capacity. PLoS One 2010, 5:1-10.
• [2]Banchereau J, Briere F, Caux C, Davoust J, Lebecque S, Liu YJ, Pulendran B, Palucka K: Immunobiology of dendritic cells. Annu Rev Immunol 2000, 18:767-811.
• [3]Banchereau J, Steinman RM: Dendritic cells and the control of immunity. Nature 1998, 392:245-252.
• [4]Kapsenberg ML: Dendritic-cell control of pathogen-driven T cell polarization. Nat Rev Immunol 2003, 3:984-993.
• [5]Bromley SK, Iaboni A, Davis SJ, Whitty A, Green JM, Shaw AS, Weiss A, Dustin ML: The immunological synapse and CD28-CD80 interactions. Nature Immunology 2001, 2:1159-1166.
• [6]Roncarolo M-G, Levings MK, Traversari C: Differentiation of T regulatory cells by immature dendritic cells. J Exp Med 2001, 193:F5-F10.
• [7]Luo B-H, Carman CV, Springer TA: Structural basis of integrin regulation and signaling. Annu Rev Immunol 2007, 25:619-647.
• [8]Matic I, Sacchi A, Rinaldi A, Melino G, Khosla C, Falasca L, Piacentini M: Characterization of transglutaminase type II role in dendritic cell differentiation and function. J Leukoc Biol 2010, 88:181-188.
• [9]Griffin M, Casadio R, Bergamini CM: Transglutaminases: nature's biological glues. Biochem J 2002, 368:377-396.
• [10]Hodrea J, Demény MA, Majai G, Sarang Z, Korponay-Szabó IR, Fésüs L: Transglutaminase 2 is expressed and active on the surface of human monocytederived dendritic cells and macrophages. Immunol Lett 2010, 130:74-81.
• [11]Dieterich W, Ehnis T, Bauer M, Donner P, Volta U, Riecken EO, Schuppan D: Identification of tissue transglutaminase as the autoantigen of coeliac disease. Nat Med 1997, 3:797-801.
• [12]Esposito C, Paparo F, Caputo I, Porta R, Salvati VM, Mazzarella G, Auricchio S, Troncone R: Expression and enzymatic activity of small intestinal tissue transglutaminase in coeliac disease. Am J Gastroenterol 2003, 98:1813-1820.
• [13]Green PHR, Cellier C: Coeliac Disease. N Engl J Med 2007, 357:1731-1743.
• [14]Jensen K, Sollid LM, Scott H, Paulsen G, Kett K, Thorsby E, Lundin KEA: Gliadin-specific T cell responses in peripheral blood of healthy individuals involve T cells restricted by the coeliac disease associated DQ2 heterodimer. Scand J Immunol 1995, 42:166-170.
• [15]O'Keeffe J, Mills K, Jackson J, Feighery C: T cell proliferation, MHC class II restriction and cytokine products of gliadin-stimulated peripheral blood mononuclear cells (PBMC). Clin Exp Immunol 1999, 117:269-276.
• [16]Folk JE, Chung SI: Molecular and catalytic properties of transglutaminases. Adv Enzymol Relat Areas Mol Biol 1973, 38:109-191.
• [17]Robinson G, Gray T: Electron microscopy. II. Practical procedures. In Theory and practice of histological techniques. 4th edition. Edited by Bancroft J, Stevens A. New York: Churchill Livingstone; 1996:585-625.
• [18]Tough DF, Sun S, Zhang X, Sprent J: Stimulation of memory T cells by cytokines. Vaccine 2000, 18:1642-8.
• [19]Sblattero D, Berti I, Trevisiol C, Marzari R, Tommasini A, Bradbury A, Fasano A, Ventura A, Not T: Human recombinant tissue transglutaminase ELISA: an innovative diagnostic assay for coeliac disease. Am J Gastroenterol 2000, 95:1253-1257.
• [20]Lutz MB, Schuler G: Immature, semi-mature and fully mature dendritic cells: which signals induce tolerance or immunity? Trends Immunol 2002, 23:445-449.
• [21]Prechtel A, Steinkasserer A: CD83: an update on functions and prospects of the maturation marker of dendritic cells. Arch Dermatol Res 2007, 299:59-69.
• [22]Swetman CA, Leverrier Y, Garg R, Gan CH, Ridley AJ, Katz DR, Chain BM: Extension retraction and contraction in the formation of a dendritic cell dendrite: distinct roles for Rho GTPases. Eur J Immunol 2002, 32:2074-2083.
• [23]Liew FY: TH1 and TH2 cells: a historical perspective. Nat Rev Immunol 2002, 2:55-60.
• [24]Asseman C, Mauze S, Leach MW, Coffman RL, Powrie F: An Essential Role for Interleukin 10 in the Function of Regulatory T Cells That Inhibit Intestinal Inflammation. J Exp Med 1999, 190:995-1004.
• [25]Stockinger B, Veldhoen M, Martin B: Th17 T cells: Linking innate and adaptive immunity. Semin Immunol 2007, 19:353-361.
• [26]Greenberg CS, Birckbichler PJ, Rice RH: Transglutaminases: multifunctional cross-linking enzymes that stabilize tissues. FASEB J 1991, 5:3071-3077.
• [27]Bollyky PL, Falk BA, Wu RP, Buckner JH, Wight TN, Nepom GT: Intact extracellular matrix and the maintenance of immune tolerance: high molecular weight hyaluronan promotes persistence of induced CD4 + CD25+ regulatory T cells. J Leukoc Biol 2009, 86:567-572.
• [28]Zemskov EA, Janiak A, Hang J, Waghray A, Belkin AM: The role of tissue transglutaminase in cell-matrix interactions. Front Biosci 2006, 11:1057-1076.
• [29]Brown KA, Bedford P, Macey M, McCarthy DA, Leroy F, Vora AJ, Stagg AJ, Dumonde DC, Knight SC: Human blood dendritic cells: binding to vascular endothelium and expression of adhesion molecules. Clin Exp Immunol 2003, 107:601-607.
• [30]Acharya AP, Dolgova NV, Moore NM, Xia CQ, Clare-Salzler MJ, Becker ML, Gallant ND, Keselowsky BG: The modulation of dendritic cell integrin binding and activation by RGD-peptide density gradient substrates. Biomaterials 2010, 31:7444-7454.
• [31]Andersen CAS, Handley M, Pollara G, Ridley AJ, Katz DR, Chain BM: Beta 1 integrins determine the dendritic morphology which enhances DC-SIGN-mediated particle capture by dendritic cells. Int Immunol 2006, 18:1295-1303.
• [32]Telci D, Wang Z, Xiaoling L, Verderio EAM, Humphries MJ, Baccarini M, Basaga H, Griffin M: Fibronectin-Tissue transglutaminase matrix rescues RGD-impaired cell adhesion through syndecan-4 and β1 integrin co-signalling. J Biol Chem 2008, 283:20937-20947.
• [33]Nunes I, Gleizes P, Metz CN, Rifkin DB: Latent transforming growth factor-β binding protein domains involved in activation and transglutaminase-dependent cross-linking of latent transforming growth factor-β. J Cell Biol 1997, 136:1151-1163.
• [34]Troncone R, Maurano F, Rossi M, Micillo M, Greco L, Auricchio R, Salerno G, Salvatore F, Sacchetti L: IgA antibodies to tissue transglutaminase: An effective diagnostic test for coeliac disease. J Paediatrics 1999, 134:166-171.
• [35]Sollid LM: Molecular Basis of Coeliac Disease. Annu Rev Immunol 2000, 18:53-81.
• [36]Mowat AM: Anatomical basis of tolerance and immunity to intestinal antigens. Nat Rev Immunol 2003, 3:331-341.