IL-6 promotes immune responses in human ulcerative colitis and induces a skin-homing phenotype in the dendritic cells and Tcells they stimulate

European Journal of Immunology

Volumn 42, Issue 5, 2012, Pages 1337-1353

  Bernardo, David ^a   Vallejo Díez, Sara ^b   Mann, Elizabeth R ^a   Al Hassi, Hafid O ^a   Martínez Abad, Beatriz ^b   Montalvillo, Enrique ^b   Tee, Cheng T ^a   Murugananthan, Aravinth U ^a   Núñez, Henar ^c   Peake, Simon T C ^a   Hart, Ailsa L ^d   Fernández Salazar, Luis ^e   Garrote, Jose A ^c   Arranz, Eduardo ^b   Knight, Stella C ^a  

^a IMPERIAL COLLEGE LONDON   (United Kingdom)

^b UNIVERSITY OF VALLADOLID   (Spain)

^c HOSPITAL UNIVERSITARIO RÍO HORTEGA   (Spain)

^d ST MARK S HOSPITAL   (United Kingdom)

^e HOSPITAL CLÍNICO UNIVERSITARIO DE VALLADOLID   (Spain)

Author keywords

Dendritic cells; IL 6; Intestinal immunity; Mucosal immunity; Ulcerative colitis

Indexed keywords

CHEMOKINE RECEPTOR CCR8; GAMMA INTERFERON; INTERLEUKIN 13; INTERLEUKIN 4; INTERLEUKIN 6; INTERLEUKIN 7; TUMOR NECROSIS FACTOR ALPHA;

ARTICLE; CELLULAR IMMUNITY; COLON BIOPSY; CONTROLLED STUDY; CYTOKINE PRODUCTION; CYTOKINE RELEASE; CYTOKINE RESPONSE; DENDRITIC CELL; DISEASE SEVERITY; EFFECTOR CELL; ENDOSCOPY; FEMALE; HUMAN; HUMAN CELL; HUMAN TISSUE; IMMUNOMODULATION; IMMUNOSTIMULATION; IN VITRO STUDY; INTESTINE MUCOSA; LIMIT OF DETECTION; MALE; MUCOSAL IMMUNITY; PHENOTYPE; PRIORITY JOURNAL; PROTEIN EXPRESSION; SUPERNATANT; TH2 CELL; ULCERATIVE COLITIS;

ADULT; AGED; AGED, 80 AND OVER; CELLS, CULTURED; COLITIS, ULCERATIVE; CYTOKINES; DENDRITIC CELLS; FEMALE; HUMANS; INFLAMMATION; INTERLEUKIN-13; INTERLEUKIN-6; MALE; MIDDLE AGED; SEVERITY OF ILLNESS INDEX; SKIN; T-LYMPHOCYTES; TH2 CELLS;

EID: 84860333121     PISSN: 00142980     EISSN: 15214141     Source Type: Journal    
DOI: 10.1002/eji.201142327     Document Type: Article

References (57)

1. Mowat, A. M., Anatomical basis of tolerance and immunity to intestinal antigens. Nat. Rev. Immunol. 2003. 3: 331-341.
2. Heller, F., Florian, P., Bojarski, C., Richter, J., Christ, M., Hillenbrand, B., Mankertz, J. et al., Interleukin-13 is the key effector Th2 cytokine in ulcerative colitis that affects epithelial tight junctions, apoptosis, and cell restitution. Gastroenterology 2005. 129: 550-564.
3. Strober, W. and Fuss, I. J., Proinflammatory cytokines in the pathogenesis of inflammatory bowel diseases. Gastroenterology 2011. 140: 1756-1767.
4. Larsen, S., Bendtzen, K. and Nielsen, O. H., Extraintestinal manifestations of inflammatory bowel disease: epidemiology, diagnosis, and management. Ann. Med. 2010. 42: 97-114.
5. Veloso, F. T., Extraintestinal manifestations of inflammatory bowel disease: do they influence treatment and outcome? World J. Gastroenterol. 2011. 17: 2702-2707.
6. Banchereau, J. and Steinman, R. M., Dendritic cells and the control of immunity. Nature 1998. 392: 245-252.
7. Niess, J. H. and Reinecker, H. C., Dendritic cells: the commanders-in-chief of mucosal immune defenses. Curr. Opin. Gastroenterol. 2006. 22: 354-360.
8. Hart, A. L., Al-Hassi, H. O., Rigby, R. J., Bell, S. J., Emmanuel, A. V., Knight, S. C., Kamm, M. A. et al., Characteristics of intestinal dendritic cells in inflammatory bowel diseases. Gastroenterology 2005. 129: 50-65.
9. Chirdo, F. G., Millington, O. R., Beacock-Sharp, H. and Mowat, A. M., Immunomodulatory dendritic cells in intestinal lamina propria. Eur. J. Immunol. 2005. 35: 1831-1840.
10. Coombes, J. L., Siddiqui, K. R., Arancibia-Cárcamo, C. V., Hall, J., Sun, C. M., Belkaid, Y. and Powrie, F., A functionally specialized population of mucosal CD103+ DCs induces Foxp3+ regulatory T cells via a TGF-beta and retinoic acid-dependent mechanism. J. Exp. Med. 2007. 204: 1757-1764.
11. Stagg, A. J., Kamm, M. A. and Knight, S. C., Intestinal dendritic cells increase T-cell expression of alpha4beta7 integrin. Eur. J. Immunol. 2002. 32: 1445-1454.
12. von Boehmer, H., Oral tolerance: is it all retinoic acid? J. Exp. Med. 2007. 204: 1737-1739.
13. Sigmundsdottir, H. and Butcher, E. C., Environmental cues, dendritic cells and the programming of tissue-selective lymphocyte trafficking. Nat. Immunol. 2008. 9: 981-987.
14. Mora, J. R., Iwata, M. and von Andrian, U. H., Vitamin effects on the immune system: vitamins A and D take centre stage. Nat. Rev. Immunol. 2008. 8: 685-698.
15. Mora, J. R., Iwata, M., Eksteen, B., Song, S. Y., Junt, T., Senman, B., Otipoby, K. L. et al., Generation of gut-homing IgA-secreting B cells by intestinal dendritic cells. Science 2006. 314: 1157-1160.
16. Iwata, M., Hirakiyama, A., Eshima, Y., Kagechika, H., Kato, C. and Song, S. Y., Retinoic acid imprints gut-homing specificity on T cells. Immunity 2004. 21: 527-538.
17. Mora, J. R. and von Andrian, U. H., Role of retinoic acid in the imprinting of gut-homing IgA-secreting cells. Semin. Immunol. 2009. 21: 28-35.
18. Hadis, U., Wahl, B., Schulz, O., Hardtke-Wolenski, M., Schippers, A., Wagner, N., Müller, W. et al., Intestinal tolerance requires gut homing and expansion of FoxP3+ regulatory T cells in the lamina propria. Immunity 2011. 34: 237-246.
19. La Cava, A., Van Kaer, L. and Fu-Dong-Shi CD4+CD25+ Tregs and NKT cells: regulators regulating regulators. Trends Immunol. 2006. 27: 322-327.
20. Seino, K. and Taniguchi, M., Functionally distinct NKT-cell subsets and subtypes. J. Exp. Med. 2005. 202: 1623-1626.
21. Kim, H. J., Hwang, S. J., Kim, B. K., Jung, K. C. and Chung, D. H., NKT cells play critical roles in the induction of oral tolerance by inducing regulatory T cells producing IL-10 and transforming growth factor beta, and by clonally deleting antigen-specific T cells. Immunology 2006. 118: 101-111.
22. Rimoldi, M., Chieppa, M., Salucci, V., Avogadri, F., Sonzogni, A., Sampietro, G. M., Nespoli, A. et al., Intestinal immune homeostasis is regulated by the crosstalk between epithelial cells and dendritic cells. Nat. Immunol. 2005. 6: 507-514.
23. Butler, M., Ng, C. Y., van Heel, D. A., Lombardi, G., Lechler, R., Playford, R. J. and Ghosh, S., Modulation of dendritic cell phenotype and function in an in vitro model of the intestinal epithelium. Eur. J. Immunol. 2006. 36: 864-874.
24. Iliev, I. D., Mileti, E., Matteoli, G., Chieppa, M. and Rescigno, M., Intestinal epithelial cells promote colitis-protective regulatory T-cell differentiation through dendritic cell conditioning. Mucosal. Immunol. 2009. 2: 340-350.
25. Iliev, I. D., Spadoni, I., Mileti, E., Matteoli, G., Sonzogni, A., Sampietro, G. M., Foschi, D. et al., Human intestinal epithelial cells promote the differentiation of tolerogenic dendritic cells. Gut 2009. 58: 1481-1489.
26. Mann, E. R., Bernardo, D., Al-Hassi, H. O., English, N. R., Clark, S. K., McCarthy, N. E., Milestone, A. N., et al. In humans, gut-specific homeostatic dendritic cells are generated from blood precursors by the gut microenvironment. Inflamm. Bowel Dis. 2011. In press.
27. León, A. J., Gómez, E., Garrote, J. A., Bernardo, D., Barrera, A., Marcos, J. L., Fernández-Salazar, L. et al., High levels of proinflammatory cytokines, but not markers of tissue injury, in unaffected intestinal areas from patients with IBD. Mediators Inflamm. 2009. 2009: 580450.
28. Dudda, J. C., Lembo, A., Bachtanian, E., Huehn, J., Siewert, C., Hamann, A., Kremmer, E. et al., Dendritic cells govern induction and reprogramming of polarized tissue-selective homing receptor patterns of T cells: important roles for soluble factors and tissue microenvironments. Eur. J. Immunol. 2005. 35: 1056-1065.
29. Huff, K. R., Akhtar, L. N., Fox, A. L., Cannon, J. A., Smith, P. D. and Smythies, L. E., Extracellular matrix-associated cytokines regulate CD4+ effector T-cell responses in the human intestinal mucosa. Mucosal. Immunol. 2011. 4: 420-427.
30. Bogunovic, M., Ginhoux, F., Helft, J., Shang, L., Hashimoto, D., Greter, M., Liu, K. et al., Origin of the lamina propria dendritic cell network. Immunity 2009. 31: 513-525.
31. Varol, C., Vallon-Eberhard, A., Elinav, E., Aychek, T., Shapira, Y., Luche, H., Fehling, H. J. et al., Intestinal lamina propria dendritic cell subsets have different origin and functions. Immunity 2009. 31: 502-512.
32. Schulz, O., Jaensson, E., Persson, E. K., Liu, X., Worbs, T., Agace, W. W. et al., Intestinal CD103+, but not CX3CR1+, antigen sampling cells migrate in lymph and serve classical dendritic cell functions. J. Exp. Med. 2009. 206: 3101-3114.
33. Laffont, S., Siddiqui, K. R. and Powrie, F., Intestinal inflammation abrogates the tolerogenic properties of MLN CD103+ dendritic cells. Eur. J. Immunol. 2010. 40: 1877-1883.
34. hi monocytes from antiinflammatory macrophages to inflammatory dendritic cells in the colon. J. Exp. Med. 2012. 209: 139--55.
35. DePaolo, R. W., Abadie, V., Tang, F., Fehlner-Peach, H., Hall, J. A., Wang, W., Marietta, E. V. et al., Co-adjuvant effects of retinoic acid and IL-15 induce inflammatory immunity to dietary antigens. Nature 2011. 471: 220-224.
36. Bernardo, D., van Hoogstraten, I. M., Verbeek, W. H., Peña, A. S., Mearin, M. L., Arranz, E., Garrote, J. A. et al., Decreased circulating iNKT-cell numbers in refractory coeliac disease. Clin. Immunol. 2008. 126: 172-179.
37. Arihiro, S., Ohtani, H., Suzuki, M., Murata, M., Ejima, C., Oki, M., Kinouchi, Y. et al., Differential expression of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) in ulcerative colitis and Crohn's disease. Pathol. Int. 2002. 52: 367-374.
38. Hart, A. L., Kamm, M. A., Knight, S. C. and Stagg, A. J., Quantitative and functional characteristics of intestinal-homing memory T cells: analysis of Crohn's disease patients and healthy controls. Clin. Exp. Immunol. 2004. 135: 137-145.
39. Hart, A. L., Kamm, M. A., Knight, S. C. and Stagg, A. J., Prospective evaluation of intestinal homing memory T cells in ulcerative colitis. Inflamm. Bowel Dis. 2004. 10: 496-503.
40. Kawashima, R., Kawamura, Y. I., Oshio, T., Son, A., Yamazaki, M., Hagiwara, T., Okada, T. et al., Interleukin-13 damages intestinal mucosa via TWEAK and Fn14 in mice-a pathway associated with ulcerative colitis. Gastroenterology 2011. 141: 2119-2129.
41. Gibbons, D. L. and Spencer, J., Mouse and human intestinal immunity: same ballpark, different players; different rules, same score. Mucosal. Immunol. 2011. 4: 148-157.
42. Inoue, S., Matsumoto, T., Iida, M., Mizuno, M., Kuroki, F., Hoshika, K. and Shimizu, M., Characterization of cytokine expression in the rectal mucosa of ulcerative colitis: correlation with disease activity. Am. J. Gastroenterol. 1999. 94: 2441-2446.
43. Bernardo, D., Garrote, J. A., Allegretti, Y., León, A., Gómez, E., Bermejo-Martin, J. F., Calvo, C. et al., Higher constitutive IL15R alpha expression and lower IL-15 response threshold in coeliac disease patients. Clin. Exp. Immunol. 2008. 154: 64-73.
44. Sanchez-Munoz, F., Dominguez-Lopez, A., and Yamamoto-Furusho, J. K., Role of cytokines in inflammatory bowel disease. World J. Gastroenterol. 2008. 14: 4280-4288.
45. Li, Y., de Haar, C., Chen, M., Deuring, J., Gerrits, M. M., Smits, R., Xia, B. et al., Disease-related expression of the IL6/STAT3/SOCS3 signallng pathway in ulcerative colitis and ulcerative colitis-related carcinogenesis. Gut 2010. 59: 227-235.
46. Brand, S., Crohn's disease: th1, Th17 or both? The change of a paradigm: new immunological and genetic insights implicate Th17 cells in the pathogenesis of Crohn's disease. Gut 2009. 58: 1152-1167.
47. Olsen, T., Rismo, R., Cui, G., Goll, R., Christiansen, I. and Florholmen, J., TH1 and TH17 interactions in untreated inflamed mucosa of inflammatory bowel disease, and their potential to mediate the inflammation. Cytokine. 2011. 56: 633-640.
48. Nishimoto, N. and Kishimoto, T., Humanized antihuman IL-6 receptor antibody, tocilizumab. Handb. Exp. Pharmacol. 2008. 181: 151-160.
49. Kitamura, K., Nakamoto, Y., Kaneko, S. and Mukaida, N., Pivotal roles of interleukin-6 in transmural inflammation in murine T-cell transfer colitis. J. Leukoc. Biol. 2004. 76: 1111-1117.
50. Mitsuyama, K., Matsumoto, S., Masuda, J., Yamasakii, H., Kuwaki, K., Takedatsu, H. and Sata, M., Therapeutic strategies for targeting the IL-6/STAT3 cytokine signaling pathway in inflammatory bowel disease. Anticancer Res. 2007. 27: 3749-3756.
51. Holden, N. J., Bedford, P. A., McCarthy, N. E., Marks, N. A., Ind, P. W., Jowsey, I. R., Basketter, D. A.et al., Dendritic cells from control but not atopic donors respond to contact and respiratory sensitizer treatment in vitro with differential cytokine production and altered stimulatory capacity. Clin. Exp. Allergy 2008. 38: 1148-1159.
52. Ng, S. C., Plamondon, S., Al-Hassi, H. O., English, N., Gellatly, N., Kamm, M. A., Knight, S. C. et al., A novel population of human CD56+ human leucocyte antigen D-related (HLA-DR+) colonic lamina propria cells is associated with inflammation in ulcerative colitis. Clin. Exp. Immunol. 2009. 158: 205-218.
53. Bagwell, C. B., Hyperlog-a flexible log-like transform for negative, zero, and positive valued data. Cytometry A 2005. 64: 34-42.
54. Ren, M., Pozzi, S., Bistulfi, G., Somenzi, G., Rossetti, S. and Sacchi, N., Impaired retinoic acid (RA) signal leads to RARbeta2 epigenetic silencing and RA resistance. Mol. Cell Biol. 2005. 25: 10591-10603.
55. Ozbek, S. M., Ozbek, A. and Erdorgan, A. S., Analysis of Enterococcus faecalis in samples from Turkish patients with primary endodontic infections and failed endodontic treatment by real-time PCR SYBR green method. J. Appl. Oral Sci. 2009. 17: 370-374.
56. Lundgren, A., Strömberg, E., Sjöling, A., Lindholm, C., Enarsson, K., Edebo, A., Johnsson, E. et al., Mucosal FOXP3-expressing CD4+ CD25high regulatory T cells in Helicobacter pylori-infected patients. Infect. Immun. 2005. 73: 523-531.
57. Ferreyra Solari, N. E., Galoppo, C., Cuarterolo, M., Goñi, J., Fernández-Salazar, L., Arranz, L. E., Garrote, J. A. et al., The simultaneous high expression of Vα24, IFN-γ and FoxP3 characterizes the liver of children with type I autoimmune hepatitis. Clin. Immunol. 2010. 137: 396-405.