Absence of a role for interleukin-13 in inflammatory bowel disease

被引:90
作者
Biancheri, Paolo [1 ,2 ]
Di Sabatino, Antonio [2 ]
Ammoscato, Francesca [1 ]
Facciotti, Federica [3 ]
Caprioli, Flavio [4 ,5 ]
Curciarello, Renata [1 ]
Hoque, Syed S. [1 ]
Ghanbari, Amir [1 ]
Joe-Njoku, Ijeoma [1 ]
Giuffrida, Paolo [1 ]
Rovedatti, Laura [2 ]
Geginat, Jens [3 ]
Corazza, Gino R. [2 ]
MacDonald, Thomas T. [1 ]
机构
[1] Barts & London Queen Marys Sch Med & Dent, Blizard Inst, Ctr Immunol & Infect Dis, London E1 2AT, England
[2] Univ Pavia, Dept Internal Med, S Matteo Hosp, Ctr Studio & Cura Malattie Infiammatorie Cron Int, I-27100 Pavia, Italy
[3] Ist Nazl Genet Mol, Milan, Italy
[4] Fdn IRCCS Ca Granda Osped Maggiore Policlin, Unit Gastroenterol 2, Milan, Italy
[5] Univ Milan, Dipartimento Fisiopatol Med Chirurg & Trapianti, Milan, Italy
关键词
Crohn's disease; Fibrosis; T helper cell type 2; Ulcerative colitis; GROWTH-FACTOR-BETA; ULCERATIVE-COLITIS; CROHNS-DISEASE; T-CELLS; MATRIX METALLOPROTEINASES; TGF-BETA-1; PRODUCTION; DENDRITIC CELLS; MUCOSA; EXPRESSION; INDUCTION;
D O I
10.1002/eji.201343524
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
071005 [微生物学]; 100108 [医学免疫学];
摘要
IL-13 has been implicated in the pathogenesis of ulcerative colitis (UC), and may have a role in animal models of gut fibrosis. We studied the involvement of IL-13 in inflammation and fibrosis in UC and Crohn's disease (CD). Intestinal biopsies and anti-CD3/CD28- or anti-CD2/CD28-stimulated lamina propria mononuclear cells from UC and CD patients and control subjects were cultured, and IL-13, IL-4, IL-5, IL-17A and IFN- production was measured. Mucosal IL-13-producing cells were characterised by flow cytometry. Gut explants from strictured CD, non-strictured CD and healthy donors were cultured ex vivo, and secreted IL-13, IL-1 and collagen were measured. IL-13 production by mucosal explants and activated lamina propria mononuclear cells did not differ between CD, UC and control subjects, and was at least a log lower than IFN- and IL-17A. IL-13-producing cells, and in particular natural killer T cells, were uniformly low in all groups. IL-4 and IL-5 were undetectable in culture supernatants. Explants of CD strictures produced low amounts of IL-13, whereas IL-1 and collagen were elevated. We could not confirm that UC or strictured CD are associated with elevated IL-13 production. These data suggest that an anti-IL-13 Ab would not be an appropriate therapeutic strategy in inflammatory bowel disease.
引用
收藏
页码:370 / 385
页数:16
相关论文
共 39 条
[1]
Interleukin-4-and-13-induced hypercontractility of human intestinal muscle cells-implication for motility changes in Crohn's disease [J].
Akiho, H ;
Lovato, P ;
Deng, YK ;
Ceponis, PJM ;
Blennerhassett, P ;
Collins, SM .
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 2005, 288 (04) :G609-G615
[2]
Phenotypic and functional features of human Th17 cells [J].
Annunziato, Francesco ;
Cosmi, Lorenzo ;
Santarlasci, Veronica ;
Maggi, Laura ;
Liotta, Francesco ;
Mazzinghi, Benedetta ;
Parente, Eliana ;
Fili, Lucia ;
Ferri, Simona ;
Frosali, Francesca ;
Giudici, Francesco ;
Romagnani, Paola ;
Parronchi, Paola ;
Tonelli, Francesco ;
Maggi, Enrico ;
Romagnani, Sergio .
JOURNAL OF EXPERIMENTAL MEDICINE, 2007, 204 (08) :1849-1861
[3]
IL-13 Promotes Collagen Accumulation in Crohn's Disease Fibrosis by Down-Regulation of Fibroblast MMP Synthesis: A Role for Innate Lymphoid Cells? [J].
Bailey, Jennifer R. ;
Bland, Paul W. ;
Tarlton, John F. ;
Peters, Iain ;
Moorghen, Moganaden ;
Sylvester, Paul A. ;
Probert, Christopher S. J. ;
Whiting, Christine V. .
PLOS ONE, 2012, 7 (12)
[4]
IL-6 promotes immune responses in human ulcerative colitis and induces a skin-homing phenotype in the dendritic cells and Tcells they stimulate [J].
Bernardo, David ;
Vallejo-Diez, Sara ;
Mann, Elizabeth R. ;
Al-Hassi, Hafid O. ;
Martinez-Abad, Beatriz ;
Montalvillo, Enrique ;
Tee, Cheng T. ;
Murugananthan, Aravinth U. ;
Nunez, Henar ;
Peake, Simon T. C. ;
Hart, Ailsa L. ;
Fernandez-Salazar, Luis ;
Garrote, Jose A. ;
Arranz, Eduardo ;
Knight, Stella C. .
EUROPEAN JOURNAL OF IMMUNOLOGY, 2012, 42 (05) :1337-1353
[5]
BEST WR, 1976, GASTROENTEROLOGY, V70, P439
[6]
Fibrogenesis in Crohn's disease [J].
Burke, John P. ;
Mulsow, Jurgen J. ;
O'Keane, Conor ;
Docherty, Neil G. ;
Watson, R. William G. ;
O'Connell, P. Ronan .
AMERICAN JOURNAL OF GASTROENTEROLOGY, 2007, 102 (02) :439-448
[7]
Interleukins 4 and 13 increase intestinal epithelial permeability by a phosphatidylinositol 3-kinase pathway - Lack of evidence for STAT 6 involvement [J].
Ceponis, PJM ;
Botelho, F ;
Richards, CD ;
McKay, DM .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (37) :29132-29137
[8]
TGF-β1 production in inflammatory bowel disease:: differing production patterns in Crohn's disease and ulcerative colitis [J].
Del Zotto, B ;
Mumolo, G ;
Pronio, AM ;
Montesani, C ;
Tersigni, R ;
Boirivant, M .
CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 2003, 134 (01) :120-126
[9]
Transforming growth factor β signalling and matrix metalloproteinases in the mucosa overlying Crohn's disease strictures [J].
Di Sabatino, A. ;
Jackson, C. L. ;
Pickard, K. M. ;
Buckley, M. ;
Rovedatti, L. ;
Leakey, N. A. B. ;
Picariello, L. ;
Cazzola, P. ;
Monteleone, G. ;
Tonelli, F. ;
Corazza, G. R. ;
MacDonald, T. T. ;
Pender, S. L. .
GUT, 2009, 58 (06) :777-789
[10]
Evidence for the role of interferon-alfa production by dendritic cells in the Th1 response in celiac disease [J].
Di Sabatino, Antonio ;
Pickard, Karen M. ;
Gordon, John N. ;
Salvati, Virginia ;
Mazzarella, Giuseppe ;
Beattie, Robert M. ;
Vossenkaemper, Anna ;
Rovedatti, Laura ;
Leakey, Nicholas A. B. ;
Croft, Nicholas M. ;
Troncone, Riccardo ;
Corazza, Gino R. ;
Stagg, Andrew J. ;
Monteleone, Giovanni ;
MacDonald, Thomas T. .
GASTROENTEROLOGY, 2007, 133 (04) :1175-1187