Multifaceted activities of CCR7 regulate T-cell homeostasis in health and disease

European Journal of Immunology

Volumn 42, Issue 8, 2012, Pages 1949-1955

  Moschovakis, Georgios Leandros ^a   Förster, Reinhold ^a  

^a HANNOVER MEDICAL SCHOOL   (Germany)

Author keywords

CCL21; CCR7; Ectopic lymphoid tissue; Rheumatoid arthritis; T cell homeostasis

Indexed keywords

CHEMOKINE RECEPTOR CCR7;

CELL ACTIVITY; CELLULAR IMMUNITY; CHRONIC INFLAMMATION; HOMEOSTASIS; HUMAN; NONHUMAN; PRIORITY JOURNAL; PROTEIN FUNCTION; REVIEW; SIGNAL TRANSDUCTION; T LYMPHOCYTE; T LYMPHOCYTE ACTIVATION;

ANIMALS; ARTHRITIS, RHEUMATOID; CELL MOVEMENT; CHEMOTAXIS, LEUKOCYTE; HOMEOSTASIS; HUMANS; INFLAMMATION; LYMPH NODES; LYMPHOCYTE ACTIVATION; RECEPTORS, CCR7; SIGNAL TRANSDUCTION; T-LYMPHOCYTES;

EID: 84864744750     PISSN: 00142980     EISSN: 15214141     Source Type: Journal    
DOI: 10.1002/eji.201242614     Document Type: Review

References (75)

1. Forster, R., Davalos-Misslitz, A. C. and Rot, A., CCR7 and its ligands: balancing immunity and tolerance. Nat. Rev. Immunol. 2008. 8: 362-371.
2. Tal, O., Lim, H. Y., Gurevich, I., Milo, I., Shipony, Z., Ng, L. G., Angeli, V. et al., DC mobilization from the skin requires docking to immobilized CCL21 on lymphatic endothelium and intralymphatic crawling. J. Exp. Med. 2011. 208: 2141-2153.
3. Luster, A. D., The role of chemokines in linking innate and adaptive immunity. Curr. Opin. Immunol. 2002. 14: 129-135.
4. Link, A., Vogt, T. K., Favre, S., Britschgi, M. R., Acha-Orbea, H., Hinz, B., Cyster, J. G. et al., Fibroblastic reticular cells in lymph nodes regulate the homeostasis of naive T cells. Nat. Immunol. 2007. 8: 1255-1265.
5. Stoll, S., Delon, J., Brotz, T. M. and Germain, R. N., Dynamic imaging of T cell-dendritic cell interactions in lymph nodes. Science 2002. 296: 1873-1876.
6. Moussion, C. and Girard, J. P., Dendritic cells control lymphocyte entry to lymph nodes through high endothelial venules. Nature 2011. 479: 542-546.
7. Wendland, M., Willenzon, S., Kocks, J., Davalos-Misslitz, A. C., Hammerschmidt, S. I., Schumann, K., Kremmer, E. et al., Lymph node T cell homeostasis relies on steady state homing of dendritic cells. Immunity 2011. 35: 945-957.
8. Bruhl, H., Mack, M., Niedermeier, M., Lochbaum, D., Scholmerich, J. and Straub, R. H., Functional expression of the chemokine receptor CCR7 on fibroblast-like synoviocytes. Rheumatology 2008. 47: 1771-1774.
9. Burman, A., Haworth, O., Hardie, D. L., Amft, E. N., Siewert, C., Jackson, D. G., Salmon, M. et al., A chemokine-dependent stromal induction mechanism for aberrant lymphocyte accumulation and compromised lymphatic return in rheumatoid arthritis. J. Immunol. 2005. 174: 1693-1700.
10. Weninger, W., Carlsen, H. S., Goodarzi, M., Moazed, F., Crowley, M. A., Baekkevold, E. S., Cavanagh, L. L. et al., Naive T cell recruitment to nonlymphoid tissues: a role for endothelium-expressed CC chemokine ligand 21 in autoimmune disease and lymphoid neogenesis. J. Immunol. 2003. 170: 4638-4648.
11. Hopken, U. E., Wengner, A. M., Loddenkemper, C., Stein, H., Heimesaat, M. M., Rehm, A. and Lipp, M., CCR7 deficiency causes ectopic lymphoid neogenesis and disturbed mucosal tissue integrity. Blood 2007. 109: 886-895.
12. Wengner, A. M., Hopken, U. E., Petrow, P. K., Hartmann, S., Schurigt, U., Brauer, R. and Lipp, M., CXCR5- and CCR7-dependent lymphoid neogenesis in a murine model of chronic antigen-induced arthritis. Arthritis Rheum. 2007. 56: 3271-3283.
13. Pickens, S. R., Chamberlain, N. D., Volin, M. V., Pope, R. M., Mandelin, A. M., 2nd and Shahrara, S., Characterization of CCL19 and CCL21 in rheumatoid arthritis. Arthritis Rheum. 2011. 63: 914-922.
14. Pickens, S. R., Chamberlain, N. D., Volin, M. V., Pope, R. M., Talarico, N. E., Mandelin, A. M., 2nd and Shahrara, S., Role of the CCL21 and CCR7 pathway in rheumatoid arthritis angiogenesis. Arthritis Rheum. 2012 In press. doi: 10.1002/art.34452.
15. von Andrian, U. H. and Mackay, C. R., T-cell function and migration. Two sides of the same coin. N. Engl. J. Med. 2000. 343: 1020-1034.
16. von Andrian, U. H. and Mempel, T. R., Homing and cellular traffic in lymph nodes. Nat. Rev. Immunol. 2003. 3: 867-878.
17. Braun, A., Worbs, T., Moschovakis, G. L., Halle, S., Hoffmann, K., Bolter, J., Munk, A. et al., Afferent lymph-derived T cells and DCs use different chemokine receptor CCR7-dependent routes for entry into the lymph node and intranodal migration. Nat. Immunol. 2011. 12: 879-887.
18. Zhu, J., Yamane, H. and Paul, W. E., Differentiation of effector CD4 T cell populations. Annu. Rev. Immunol. 2010. 28: 445-489.
19. Ohl, L., Mohaupt, M., Czeloth, N., Hintzen, G., Kiafard, Z., Zwirner, J., Blankenstein, T. et al., CCR7 governs skin dendritic cell migration under inflammatory and steady-state conditions. Immunity 2004. 21: 279-288.
20. Pflicke, H. and Sixt, M., Preformed portals facilitate dendritic cell entry into afferent lymphatic vessels. J. Exp. Med. 2009. 206: 2925-2935.
21. Sanchez-Sanchez, N., Riol-Blanco, L., de la Rosa, G., Puig-Kroger, A., Garcia-Bordas, J., Martin, D., Longo, N. et al., Chemokine receptor CCR7 induces intracellular signaling that inhibits apoptosis of mature dendritic cells. Blood 2004. 104: 619-625.
22. Hendriks, H. R. and Eestermans, I. L., Disappearance and reappearance of high endothelial venules and immigrating lymphocytes in lymph nodes deprived of afferent lymphatic vessels: a possible regulatory role of macrophages in lymphocyte migration. Eur. J. Immunol. 1983. 13: 663-669.
23. Mebius, R. E., Streeter, P. R., Breve, J., Duijvestijn, A. M. and Kraal, G., The influence of afferent lymphatic vessel interruption on vascular addressin expression. J. Cell Biol. 1991. 115: 85-95.
24. Webster, B., Ekland, E. H., Agle, L. M., Chyou, S., Ruggieri, R. and Lu, T. T., Regulation of lymph node vascular growth by dendritic cells. J. Exp. Med. 2006. 203: 1903-1913.
25. Chyou, S., Ekland, E. H., Carpenter, A. C., Tzeng, T. C., Tian, S., Michaud, M., Madri, J. A. et al., Fibroblast-type reticular stromal cells regulate the lymph node vasculature. J. Immunol. 2008. 181: 3887-3896.
26. + cells and then by T and B cells. J. Immunol. 2011. 187: 5558-5567.
27. Browning, J. L., Allaire, N., Ngam-Ek, A., Notidis, E., Hunt, J., Perrin, S. and Fava, R. A., Lymphotoxin-beta receptor signaling is required for the homeostatic control of HEV differentiation and function. Immunity 2005. 23: 539-550.
28. Tzeng, T. C., Chyou, S., Tian, S., Webster, B., Carpenter, A. C., Guaiquil, V. H. and Lu, T. T., CD11c(hi) dendritic cells regulate the re-establishment of vascular quiescence and stabilization after immune stimulation of lymph nodes. J. Immunol. 2010. 184: 4247-4257.
29. Pham, T. H., Okada, T., Matloubian, M., Lo, C. G. and Cyster, J. G., S1P1 receptor signaling overrides retention mediated by G alpha i-coupled receptors to promote T cell egress. Immunity 2008. 28: 122-133.
30. Cyster, J. G., Chemokines, sphingosine-1-phosphate, and cell migration in secondary lymphoid organs. Annu. Rev. Immunol. 2005. 23: 127-159.
31. Schwab, S. R., Pereira, J. P., Matloubian, M., Xu, Y., Huang, Y. and Cyster, J. G., Lymphocyte sequestration through S1P lyase inhibition and disruption of S1P gradients. Science 2005. 309: 1735-1739.
32. Brinkmann, V., Billich, A., Baumruker, T., Heining, P., Schmouder, R., Francis, G., Aradhye, S. et al., Fingolimod (FTY720): discovery and development of an oral drug to treat multiple sclerosis. Nat. Rev. Drug Discov. 2010. 9: 883-897.
33. Grigorova, I. L., Schwab, S. R., Phan, T. G., Pham, T. H., Okada, T. and Cyster, J. G., Cortical sinus probing, S1P1-dependent entry and flow-based capture of egressing T cells. Nat. Immunol. 2009. 10: 58-65.
34. Friedman, R. S., Jacobelli, J. and Krummel, M. F., Surface-bound chemokines capture and prime T cells for synapse formation. Nat. Immunol. 2006. 7: 1101-1108.
35. Okada, T. and Cyster, J. G., CC chemokine receptor 7 contributes to Gi-dependent T cell motility in the lymph node. J. Immunol. 2007. 178: 2973-2978.
36. Worbs, T., Mempel, T. R., Bolter, J., von Andrian, U. H. and Forster, R., CCR7 ligands stimulate the intranodal motility of T lymphocytes in vivo. J. Exp. Med. 2007. 204: 489-495.
37. Kaiser, A., Donnadieu, E., Abastado, J. P., Trautmann, A. and Nardin, A., CC chemokine ligand 19 secreted by mature dendritic cells increases naive T cell scanning behavior and their response to rare cognate antigen. J. Immunol. 2005. 175: 2349-2356.
38. + T lymphocytes from apoptosis. Clin. Cancer Res. 2005. 11: 7901-7910.
39. + T cells. Cell Immunol. 2004. 231: 75-84.
40. + T-cell costimulation via a DOCK2/Rac-dependent pathway. Blood 2009. 114: 580-588.
41. Villalba, M., Coudronniere, N., Deckert, M., Teixeiro, E., Mas, P. and Altman, A., A novel functional interaction between Vav and PKCtheta is required for TCR-induced T-cell activation. Immunity 2000. 12: 151-160.
42. Villalba, M., Hernandez, J., Deckert, M., Tanaka, Y. and Altman, A., Vav modulation of the Ras/MEK/ERK signaling pathway plays a role in NFAT activation and CD69 upregulation. Eur. J. Immunol. 2000. 30: 1587-1596.
43. Schaeuble, K., Hauser, M. A., Singer, E., Groettrup, M. and Legler, D. F., Cross-talk between TCR and CCR7 signaling sets a temporal threshold for enhanced T lymphocyte migration. J. Immunol. 2011. 187: 5645-5652.
44. Marsland, B. J., Battig, P., Bauer, M., Ruedl, C., Lassing, U., Beerli, R. R., Dietmeier, K. et al., CCL19 and CCL21 induce a potent proinflammatory differentiation program in licensed dendritic cells. Immunity 2005. 22: 493-505.
45. Moschovakis, G. L., Bubke, A., Dittrich-Breiholz, O., Braun, A., Prinz, I., Kremmer, E. and Forster, R., Deficient CCR7 signaling promotes TH2 polarization and B-cell activation in vivo. Eur. J. Immunol. 2011. 42: 48-57.
46. Forster, R., Schubel, A., Breitfeld, D., Kremmer, E., Renner-Muller, I., Wolf, E. and Lipp, M., CCR7 coordinates the primary immune response by establishing functional microenvironments in secondary lymphoid organs. Cell 1999. 99: 23-33.
47. Grinnan, D., Sung, S. S., Dougherty, J. A., Knowles, A. R., Allen, M. B., Rose, C. E., 3rd, Nakano, H. et al., Enhanced allergen-induced airway inflammation in paucity of lymph node T cell (plt) mutant mice. J. Allergy Clin. Immunol. 2006. 118: 1234-1241.
48. Xu, B., Aoyama, K., Kusumoto, M., Matsuzawa, A., Butcher, E. C., Michie, S. A., Matsuyama, T. et al., Lack of lymphoid chemokines CCL19 and CCL21 enhances allergic airway inflammation in mice. Int. Immunol. 2007. 19: 775-784.
49. Mori, S., Nakano, H., Aritomi, K., Wang, C. R., Gunn, M. D. and Kakiuchi, T., Mice lacking expression of the chemokines CCL21-ser and CCL19 (plt mice) demonstrate delayed but enhanced T cell immune responses. J. Exp. Med. 2001. 193: 207-218.
50. Hjelmstrom, P., Fjell, J., Nakagawa, T., Sacca, R., Cuff, C. A. and Ruddle, N. H., Lymphoid tissue homing chemokines are expressed in chronic inflammation. Am. J. Pathol. 2000. 156: 1133-1138.
51. Hjelmstrom, P., Lymphoid neogenesis: de novo formation of lymphoid tissue in chronic inflammation through expression of homing chemokines. J. Leukoc. Biol. 2001. 69: 331-339.
52. Moyron-Quiroz, J. E., Rangel-Moreno, J., Kusser, K., Hartson, L., Sprague, F., Goodrich, S., et al., Role of inducible bronchus associated lymphoid tissue (iBALT) in respiratory immunity. Nat. Med. 2004. 10: 927-934.
53. Cyster, J. G., Ansel, K. M., Reif, K., Ekland, E. H., Hyman, P. L., Tang, H. L., Luther, S. A. et al., Follicular stromal cells and lymphocyte homing to follicles. Immunol. Rev. 2000. 176: 181-193.
54. Barone, F., Bombardieri, M., Manzo, A., Blades, M. C., Morgan, P. R., Challacombe, S. J., Valesini, G. et al., Association of CXCL13 and CCL21 expression with the progressive organization of lymphoid-like structures in Sjogren's syndrome. Arthritis Rheum. 2005. 52: 1773-1784.
55. Manzo, A., Paoletti, S., Carulli, M., Blades, M. C., Barone, F., Yanni, G., Fitzgerald, O. et al., Systematic microanatomical analysis of CXCL13 and CCL21 in situ production and progressive lymphoid organization in rheumatoid synovitis. Eur. J. Immunol. 2005. 35: 1347-1359.
56. Link, A., Hardie, D. L., Favre, S., Britschgi, M. R., Adams, D. H., Sixt, M., Cyster, J. G. et al., Association of T-zone reticular networks and conduits with ectopic lymphoid tissues in mice and humans. Am. J. Pathol. 2011. 178: 1662-1675.
57. Manzo, A., Bugatti, S., Caporali, R., Prevo, R., Jackson, D. G., Uguccioni, M., Buckley, C. D. et al., CCL21 expression pattern of human secondary lymphoid organ stroma is conserved in inflammatory lesions with lymphoid neogenesis. Am. J. Pathol. 2007. 171: 1549-1562.
58. Peduto, L., Dulauroy, S., Lochner, M., Spath, G. F., Morales, M. A., Cumano, A. and Eberl, G., Inflammation recapitulates the ontogeny of lymphoid stromal cells. J. Immunol. 2009. 182: 5789-5799.
59. + T cell migration within synovial tissue. Arthritis Rheum. 2003. 48: 2472-2482.
60. Buckley, C. D., Filer, A., Haworth, O., Parsonage, G. and Salmon, M., Defining a role for fibroblasts in the persistence of chronic inflammatory joint disease. Ann. Rheum. Dis. 2004. 63(Suppl 2): ii92-ii95.
61. Muller-Ladner, U., Pap, T., Gay, R. E., Neidhart, M. and Gay, S., Mechanisms of disease: the molecular and cellular basis of joint destruction in rheumatoid arthritis. Nat. Clin. Pract. Rheumatol. 2005. 1: 102-110.
62. Muller-Ladner, U., Ospelt, C., Gay, S., Distler, O. and Pap, T., Cells of the synovium in rheumatoid arthritis. Synovial fibroblasts. Arthritis Res. Ther. 2007. 9: 223.
63. Feldmann, M., Brennan, F. M. and Maini, R. N., Rheumatoid arthritis. Cell 1996. 85: 307-310.
64. Kim, K. W., Cho, M. L., Kim, H. R., Ju, J. H., Park, M. K., Oh, H. J., Kim, J. S. et al., Up-regulation of stromal cell-derived factor 1 (CXCL12) production in rheumatoid synovial fibroblasts through interactions with T lymphocytes: role of interleukin-17 and CD40L-CD40 interaction. Arthritis Rheum. 2007. 56: 1076-1086.
65. Takemura, S., Braun, A., Crowson, C., Kurtin, P. J., Cofield, R. H., O'Fallon, W. M., Goronzy, J. J. et al., Lymphoid neogenesis in rheumatoid synovitis. J. Immunol. 2001. 167: 1072-1080.
66. + T lymphocytes in rheumatoid arthritis. Eur. J. Immunol. 1998. 28: 2661-2671.
67. Sawai, H., Park, Y. W., Roberson, J., Imai, T., Goronzy, J. J. and Weyand, C. M., T cell costimulation by fractalkine-expressing synoviocytes in rheumatoid arthritis. Arthritis Rheum. 2005. 52: 1392-1401.
68. Salmon, M., Scheel-Toellner, D., Huissoon, A. P., Pilling, D., Shamsadeen, N., Hyde, H., D'Angeac, A. D. et al., Inhibition of T cell apoptosis in the rheumatoid synovium. J. Clin. Invest. 1997. 99: 439-446.
69. Pilling, D., Akbar, A. N., Girdlestone, J., Orteu, C. H., Borthwick, N. J., Amft, N., Scheel-Toellner, D. et al., Interferon-beta mediates stromal cell rescue of T cells from apoptosis. Eur. J. Immunol. 1999. 29: 1041-1050.
70. Timmer, T. C., Baltus, B., Vondenhoff, M., Huizinga, T. W., Tak, P. P., Verweij, C. L., Mebius, R. E. et al., Inflammation and ectopic lymphoid structures in rheumatoid arthritis synovial tissues dissected by genomics technology: identification of the interleukin-7 signaling pathway in tissues with lymphoid neogenesis. Arthritis Rheum. 2007. 56: 2492-2502.
71. Noss, E. H. and Brenner, M. B., The role and therapeutic implications of fibroblast-like synoviocytes in inflammation and cartilage erosion in rheumatoid arthritis. Immunol. Rev. 2008. 223: 252-270.
72. Burman, A., Haworth, O., Bradfield, P., Parsonage, G., Filer, A., Thomas, A. M., Amft, N. et al., The role of leukocyte-stromal interactions in chronic inflammatory joint disease. Joint Bone Spine 2005. 72: 10-16.
73. Gambichler, T., Skrygan, M., Labanski, A. A., Kolios, A. G., Altmeyer, P. and Kreuter, A., Significantly increased CCL5/RANTES and CCR7 mRNA levels in localized scleroderma. Regul. Pept. 2011. 170: 4-6.
74. Pierce, E. M., Carpenter, K., Jakubzick, C., Kunkel, S. L., Flaherty, K. R., Martinez, F. J. and Hogaboam, C. M., Therapeutic targeting of CC ligand 21 or CC chemokine receptor 7 abrogates pulmonary fibrosis induced by the adoptive transfer of human pulmonary fibroblasts to immunodeficient mice. Am. J. Pathol. 2007. 170: 1152-1164.
75. Muller, A., Homey, B., Soto, H., Ge, N., Catron, D., Buchanan, M. E., McClanahan, T. et al., Involvement of chemokine receptors in breast cancer metastasis. Nature 2001. 410: 50-56.