Gastroenterology
Volume 132, Issue 1 , Pages 139-153 , January 2007

Enhanced Recruitment of CX3CR1+ T Cells by Mucosal Endothelial Cell–Derived Fractalkine in Inflammatory Bowel Disease

  • Miquel Sans

      Affiliations

    • Division of Gastroenterology, University Hospitals of Cleveland, Case Western Reserve University School of Medicine, Cleveland, Ohio
    • Department of Gastroenterology, Hospital Clinic/IDIBAPS, Barcelona, Catalunya, Spain
    • ,
  • Silvio Danese

      Affiliations

    • Division of Gastroenterology, Istituto Clinico Humanitas-IRCCS in Gastroenterology, Milan, Italy
    • ,
  • Carol de la Motte

      Affiliations

    • Department of Pathobiology, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio
    • ,
  • Heitor S.P. de Souza

      Affiliations

    • Department of Pathobiology, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio
    • ,
  • Brenda M. Rivera–Reyes

      Affiliations

    • Division of Gastroenterology, University Hospitals of Cleveland, Case Western Reserve University School of Medicine, Cleveland, Ohio
    • ,
  • Gail A. West

      Affiliations

    • Department of Pathobiology, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio
    • ,
  • Manijeh Phillips

      Affiliations

    • Department of Pathobiology, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio
    • ,
  • Jeffry A. Katz

      Affiliations

    • Division of Gastroenterology, University Hospitals of Cleveland, Case Western Reserve University School of Medicine, Cleveland, Ohio
    • ,
  • Claudio Fiocchi

      Affiliations

    • Department of Pathobiology, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio
    • Corresponding Author InformationAddress requests for reprints to: Claudio Fiocchi, MD, Division of Pathobiology, Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195. fax: (216) 636-0104.

Received 14 September 2006 ,Accepted 8 November 2006.

References 

  1. Cook-Mills JM, Deem TL. Active participation of endothelial cells in inflammation. J Leukoc Biol. 2005;77:487–495
  2. Muller WA. Leukocyte-endothelial-cell interactions in leukocyte transmigration and the inflammatory response. Trends Immunol. 2003;24:327–334
  3. Panés J, Granger DN. Leukocyte-endothelial cell interactions: molecular mechanisms and implications in gastrointestinal disease. Gastroenterology. 1998;114:1066–1090
  4. Proudfoot AE, Power CA, Rommel C, Wells TN. Strategies for chemokine antagonists as therapeutics. Semin Immunol. 2003;15:57–65
  5. van Buul JD, Hordijk PL. Signaling in leukocyte transendothelial migration. Arterioscler Thromb Vasc Biol. 2004;24:824–833
  6. Papadakis KA. Chemokines in inflammatory bowel disease. Curr Allergy Asthma Rep. 2004;4:83–89
  7. Umehara H, Bloom E, Okazaki T, Domae N, Imai T. Fractalkine and vascular injury. Trends Immunol. 2001;22:602–607
  8. Haskell CA, Cleary MD, Charo IF. Unique role of the chemokine domain of fractalkine in cell capture (Kinetics of receptor dissociation correlate with cell adhesion). J Biol Chem. 2000;275:34183–34189
  9. Fong AM, Erickson HP, Zachariah JP, Poon S, Schamberg NJ, Imai T, et al. Ultrastructure and function of the fractalkine mucin domain in CX(3)C chemokine domain presentation. J Biol Chem. 2000;275:3781–3786
  10. Hundhausen C, Misztela D, Berkhout TA, Broadway N, Saftig P, Reiss K, et al. The disintegrin-like metalloproteinase ADAM10 is involved in constitutive cleavage of CX3CL1 (fractalkine) and regulates CX3CL1-mediated cell-cell adhesion. Blood. 2003;102:1186–1195
  11. Tsou CL, Haskell CA, Charo IF. Tumor necrosis factor-alpha-converting enzyme mediates the inducible cleavage of fractalkine. J Biol Chem. 2001;276:44622–44626
  12. Bazan JF, Bacon KB, Hardiman G, Wang W, Soo K, Rossi D, et al. A new class of membrane-bound chemokine with a CX3C motif. Nature. 1997;385:640–644
  13. Umehara H, Bloom ET, Okazaki T, Nagano Y, Yoshie O, Imai T. Fractalkine in vascular biology: from basic research to clinical disease. Arterioscler Thromb Vasc Biol. 2004;24:34–40
  14. Hatori K, Nagai A, Heisel R, Ryu JK, Kim SU. Fractalkine and fractalkine receptors in human neurons and glial cells. J Neurosci Res. 2002;69:418–426
  15. Cockwell P, Chakravorty SJ, Girdlestone J, Savage CO. Fractalkine expression in human renal inflammation. J Pathol. 2002;196:85–90
  16. Muehlhoefer A, Saubermann LJ, Gu X, Luedtke-Heckenkamp K, Xavier R, Blumberg RS, et al. Fractalkine is an epithelial and endothelial cell-derived chemoattractant for intraepithelial lymphocytes in the small intestinal mucosa. J Immunol. 2000;164:3368–3376
  17. Imaizumi T, Yoshida H, Satoh K. Regulation of CX3CL1/fractalkine expression in endothelial cells. J Atheroscler Thromb. 2004;11:15–21
  18. Fraticelli P, Sironi M, Bianchi G, D’Ambrosio D, Albanesi C, Stoppacciaro A, et al. Fractalkine (CX3CL1) as an amplification circuit of polarized Th1 responses. J Clin Invest. 2001;107:1173–1181
  19. Imai T, Hieshima K, Haskell C, Baba M, Nagira M, Nishimura M, et al. Identification and molecular characterization of fractalkine receptor CX3CR1, which mediates both leukocyte migration and adhesion. Cell. 1997;91:521–530
  20. Combadiere C, Salzwedel K, Smith ED, Tiffany HL, Berger EA, Murphy PM. Identification of CX3CR1 (A chemotactic receptor for the human CX3C chemokine fractalkine and a fusion coreceptor for HIV-1). J Biol Chem. 1998;273:23799–23804
  21. Haskell CA, Cleary MD, Charo IF. Molecular uncoupling of fractalkine-mediated cell adhesion and signal transduction (Rapid flow arrest of CX3CR1-expressing cells is independent of G-protein activation). J Biol Chem. 1999;274:10053–10058
  22. Greaves DR, Hakkinen T, Lucas AD, Liddiard K, Jones E, Quinn CM, et al. Linked chromosome 16q13 chemokines, macrophage-derived chemokine, fractalkine, and thymus- and activation-regulated chemokine, are expressed in human atherosclerotic lesions. Arterioscler Thromb Vasc Biol. 2001;21:923–929
  23. Furuichi K, Wada T, Iwata Y, Sakai N, Yoshimoto K, Shimizu M, et al. Upregulation of fractalkine in human crescentic glomerulonephritis. Nephron. 2001;87:314–320
  24. Robinson LA, Nataraj C, Thomas DW, Howell DN, Griffiths R, Bautch V, et al. A role for fractalkine and its receptor (CX3CR1) in cardiac allograft rejection. J Immunol. 2000;165:6067–6072
  25. Raychaudhuri SP, Jiang WY, Farber EM. Cellular localization of fractalkine at sites of inflammation: antigen-presenting cells in psoriasis express high levels of fractalkine. Br J Dermatol. 2001;144:1105–1113
  26. Nanki T, Imai T, Nagasaka K, Urasaki Y, Nonomura Y, Taniguchi K, et al. Migration of CX3CR1-positive T cells producing type 1 cytokines and cytotoxic molecules into the synovium of patients with rheumatoid arthritis. Arthritis Rheum. 2002;46:2878–2883
  27. Hasegawa M, Sato S, Echigo T, Hamaguchi Y, Yasui M, Takehara K. Up regulated expression of fractalkine/CX3CL1 and CX3CR1 in patients with systemic sclerosis. Ann Rheum Dis. 2005;64:21–28
  28. Isse K, Harada K, Zen Y, Kamihira T, Shimoda S, Harada M, et al. Fractalkine and CX3CR1 are involved in the recruitment of intraepithelial lymphocytes of intrahepatic bile ducts. Hepatology. 2005;41:506–516
  29. Brand S, Sakaguchi T, Gu X, Colgan SP, Reinecker HC. Fractalkine-mediated signals regulate cell-survival and immune-modulatory responses in intestinal epithelial cells. Gastroenterology. 2002;122:166–177
  30. Niess JH, Brand S, Gu X, Landsman L, Jung S, McCormick BA, et al. CX3CR1-mediated dendritic cell access to the intestinal lumen and bacterial clearance. Science. 2005;307:254–258
  31. Lederman S, Yellin MJ, Krichevsky A, Belko J, Lee JJ, Chess L. Identification of a novel surface protein on activated CD4+ T cells that induces contact-dependent B cell differentiation (help). J Exp Med. 1992;175:1091–1101
  32. Binion DG, West GA, Ina K, Ziats NP, Emancipator SN, Fiocchi C. Enhanced leukocyte binding by intestinal microvascular endothelial cells in inflammatory bowel disease. Gastroenterology. 1997;112:1895–1907
  33. Harvey RF, Bradshaw JM. A simple index of Crohn’s-disease activity. Lancet. 1980;1:514
  34. Sutherland LR, Martin F, Greer S, Robinson M, Greenberger N, Saibil F, et al. 5-Aminosalicylic acid enema in the treatment of distal ulcerative colitis, proctosigmoiditis, and proctitis. Gastroenterology. 1987;92:1894–1898
  35. Sturm A, Itoh J, Jacobberger JW, Fiocchi C. p53 negatively regulates intestinal immunity by delaying mucosal T cell cycling. J Clin Invest. 2002;109:1481–1492
  36. Danese S, de la Motte C, Sturm A, Vogel JD, West GA, Strong SA, et al. Platelets trigger a CD40-dependent inflammatory response in the microvasculature of inflammatory bowel disease patients. Gastroenterology. 2003;124:1249–1264
  37. Ropert C, Almeida IC, Closel M, Travassos LR, Ferguson MA, Cohen P, et al. Requirement of mitogen-activated protein kinases and I kappa B phosphorylation for induction of proinflammatory cytokines synthesis by macrophages indicates functional similarity of receptors triggered by glycosylphosphatidylinositol anchors from parasitic protozoa and bacterial lipopolysaccharide. J Immunol. 2001;166:3423–3431
  38. Thodeti CK, Albrechtsen R, Grauslund M, Asmar M, Larsson C, Takada Y, et al. ADAM12/syndecan-4 signaling promotes beta 1 integrin-dependent cell spreading through protein kinase Calpha and RhoA. J Biol Chem. 2003;278:9576–9584
  39. Feigelson SW, Grabovsky V, Winter E, Chen LL, Pepinsky RB, Yednock T, et al. The Src kinase p56(lck) up-regulates VLA-4 integrin affinity (Implications for rapid spontaneous and chemokine-triggered T cell adhesion to VCAM-1 and fibronectin). J Biol Chem. 2001;276:13891–13901
  40. Musso A, Condon TP, West GA, De La MC, Strong SA, Levine AD, et al. Regulation of ICAM-1-mediated fibroblast-T cell reciprocal interaction: implications for modulation of gut inflammation. Gastroenterology. 1999;117:546–556
  41. Vogel JD, West GA, Danese S, De La MC, Phillips MH, Strong SA, et al. CD40-mediated immune-nonimmune cell interactions induce mucosal fibroblast chemokines leading to T-cell transmigration. Gastroenterology. 2004;126:63–80
  42. Roth SJ, Carr MW, Rose SS, Springer TA. Characterization of transendothelial chemotaxis of T lymphocytes. J Immunol Methods. 1995;188:97–116
  43. Umehara H, Goda S, Imai T, Nagano Y, Minami Y, Tanaka Y, et al. Fractalkine, a CX3C-chemokine, functions predominantly as an adhesion molecule in monocytic cell line THP-1. Immunol Cell Biol. 2001;79:298–302
  44. Chapman GA, Moores KE, Gohil J, Berkhout TA, Patel L, Green P, et al. The role of fractalkine in the recruitment of monocytes to the endothelium. Eur J Pharmacol. 2000;392:189–195
  45. Papadakis KA, Targan SR. The role of chemokines and chemokine receptors in mucosal inflammation. Inflamm Bowel Dis. 2000;6:303–313
  46. Fong AM, Robinson LA, Steeber DA, Tedder TF, Yoshie O, Imai T, et al. Fractalkine and CX3CR1 mediate a novel mechanism of leukocyte capture, firm adhesion, and activation under physiologic flow. J Exp Med. 1998;188:1413–1419
  47. Constantin G, Majeed M, Giagulli C, Piccio L, Kim JY, Butcher EC, et al. Chemokines trigger immediate beta2 integrin affinity and mobility changes: differential regulation and roles in lymphocyte arrest under flow. Immunity. 2000;13:759–769
  48. Chan JR, Hyduk SJ, Cybulsky MI. Detecting rapid and transient upregulation of leukocyte integrin affinity induced by chemokines and chemoattractants. J Immunol Methods. 2003;273:43–52
  49. Mould AP, Askari JA, Barton S, Kline AD, McEwan PA, Craig SE, et al. Integrin activation involves a conformational change in the alpha 1 helix of the beta subunit A-domain. J Biol Chem. 2002;277:19800–19805
  50. Lucas AD, Chadwick N, Warren BF, Jewell DP, Gordon S, Powrie F, et al. The transmembrane form of the CX3CL1 chemokine fractalkine is expressed predominantly by epithelial cells in vivo. Am J Pathol. 2001;158:855–866
  51. Podolsky DK, Fiocchi C. Cytokines, chemokines, growth factors, eicosanoids and other bioactive molecules in IBD. In:  Kirsner JB editors. Inflammatory bowel disease. Philadelphia: W.B. Saunders; 1999;p. 191–207
  52. Bolovan-Fritts CA, Trout RN, Spector SA. Human cytomegalovirus-specific CD4+-T-cell cytokine response induces fractalkine in endothelial cells. J Virol. 2004;78:13173–13181
  53. Hommes DW, Peppelenbosch MP, van Deventer SJ. Mitogen activated protein (MAP) kinase signal transduction pathways and novel anti-inflammatory targets. Gut. 2003;52:144–151
  54. Hollenbach E, Neumann M, Vieth M, Roessner A, Malfertheiner P, Naumann M. Inhibition of p38 MAP kinase- and RICK/NF-kappaB-signaling suppresses inflammatory bowel disease. FASEB J. 2004;18:1550–1552
  55. Hollenbach E, Vieth M, Roessner A, Neumann M, Malfertheiner P, Naumann M. Inhibition of RICK/nuclear factor-kappaB and p38 signaling attenuates the inflammatory response in a murine model of Crohn disease. J Biol Chem. 2005;280:14981–14988
  56. Foussat A, Coulomb-L’Hermine A, Gosling J, Krzysiek R, Durand-Gasselin I, Schall T, et al. Fractalkine receptor expression by T lymphocyte subpopulations and in vivo production of fractalkine in human. Eur J Immunol. 2000;30:87–97
  57. Rimaniol AC, Till SJ, Garcia G, Capel F, Godot V, Balabanian K, et al. The CX3C chemokine fractalkine in allergic asthma and rhinitis. J Allergy Clin Immunol. 2003;112:1139–1146
  58. Goda S, Imai T, Yoshie O, Yoneda O, Inoue H, Nagano Y, et al. CX3C-chemokine, fractalkine-enhanced adhesion of THP-1 cells to endothelial cells through integrin-dependent and -independent mechanisms. J Immunol. 2000;164:4313–4320
  59. Kerfoot SM, Lord SE, Bell RB, Gill V, Robbins SM, Kubes P. Human fractalkine mediates leukocyte adhesion but not capture under physiological shear conditions; a mechanism for selective monocyte recruitment. Eur J Immunol. 2003;33:729–739
  60. Ancuta P, Rao R, Moses A, Mehle A, Shaw SK, Luscinskas FW, et al. Fractalkine preferentially mediates arrest and migration of CD16+ monocytes. J Exp Med. 2003;197:1701–1707
  61. Dichmann S, Herouy Y, Purlis D, Rheinen H, Gebicke-Harter P, Norgauer J. Fractalkine induces chemotaxis and actin polymerization in human dendritic cells. Inflamm Res. 2001;50:529–533
  62. Papadopoulos EJ, Fitzhugh DJ, Tkaczyk C, Gilfillan AM, Sassetti C, Metcalfe DD, et al. Mast cells migrate, but do not degranulate, in response to fractalkine, a membrane-bound chemokine expressed constitutively in diverse cells of the skin. Eur J Immunol. 2000;30:2355–2361
  63. Ancuta P, Moses A, Gabuzda D. Transendothelial migration of CD16+ monocytes in response to fractalkine under constitutive and inflammatory conditions. Immunobiology. 2004;209:11–20
  64. Johnson Z, Schwarz M, Power CA, Wells TN, Proudfoot AE. Multi-faceted strategies to combat disease by interference with the chemokine system. Trends Immunol. 2005;26:268–274
  65. Nanki T, Urasaki Y, Imai T, Nishimura M, Muramoto K, Kubota T, et al. Inhibition of fractalkine ameliorates murine collagen-induced arthritis. J Immunol. 2004;173:7010–7016
  66. Suzuki F, Nanki T, Imai T, Kikuchi H, Hirohata S, Kohsaka H, et al. Inhibition of CX3CL1 (fractalkine) improves experimental autoimmune myositis in SJL/J mice. J Immunol. 2005;175:6987–6996

 Supported by grants from the Fulbright/Generalitat de Catalunya, Ministerio de Educación y Ciencia (Programa Ramón y Cajal, SAF2005-00280 and C03/02) and Fundación Ramón Areces (M.S.), and the National Institutes of Health (DK30399 and DK 50984) (to C.F.).

PII: S0016-5085(06)02233-5

doi: 10.1053/j.gastro.2006.10.010

Gastroenterology
Volume 132, Issue 1 , Pages 139-153 , January 2007

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