Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Digestive Diseases and Sciences
Published in: Digestive Diseases and Sciences 2/2018

01-02-2018 | Invited Review

Old and New Lymphocyte Players in Inflammatory Bowel Disease

Authors: Paolo Giuffrida, Gino Roberto Corazza, Antonio Di Sabatino

Published in: Digestive Diseases and Sciences | Issue 2/2018

Login to get access

Abstract

Inflammatory bowel disease (IBD), encompassing Crohn’s disease and ulcerative colitis, is a chronic intestinal inflammatory disorder characterized by diffuse accumulation of lymphocytes in the gut mucosa as a consequence of over-expression of endothelial adhesion molecules. The infiltrating lymphocytes have been identified as subsets of T cells, including T helper (Th)1 cells, Th17 cells, and regulatory T cells. The function of these lymphocyte subpopulations in the development of IBD is well-known, since they produce a number of pro-inflammatory cytokines, such as interferon-γ and interleukin-17A, which in turn activate mucosal proteases, thus leading to the development of intestinal lesions, i.e., ulcers, fistulas, abscesses, and strictures. However, the immune mechanisms underlying IBD are not yet fully understood, and knowledge about the function of newly discovered lymphocytes, including Th9 cells, innate lymphoid cells, mucosal-associated invariant T cells, and natural killer T cells, might add new pieces to the complex puzzle of IBD pathogenesis. This review summarizes the recent advances in the understanding of the role of mucosal lymphocytes in chronic intestinal inflammation and deals with the therapeutic potential of lymphocyte-targeting drugs in IBD patients.
Literature
1.
Kaplan GG, Ng SC. Understanding and preventing the global increase of inflammatory bowel disease. Gastroenterology. 2017;152:313–321.PubMedCrossRef
2.
Ding NS, Hart A, De Cruz P. Systematic review: predicting and optimizing response to anti-TNF therapy in Crohn’s disease—algorithm for practical management. Aliment Pharmacol Ther. 2016;43:30–51.PubMedCrossRef
3.
Vermeire S, Loftus EV Jr, Colombel JF, et al. Long-term efficacy of vedolizumab for Crohn’s disease. J Crohns Colitis. 2017;11:412–424.PubMed
4.
Loftus EV Jr, Colombel JF, Feagan BG, et al. Long-term efficacy of vedolizumab for ulcerative colitis. J Crohns Colitis. 2017;11:400–411.PubMed
5.
Weigmann B, Neurath MF. Th9 cells in inflammatory bowel diseases. Semin Immunopathol. 2017;39:89–95.PubMedCrossRef
6.
Goldberg R, Prescott N, Lord GM, MacDonald TT, Powell N. The unusual suspects—innate lymphoid cells as novel therapeutic targets in IBD. Nat Rev Gastroenterol Hepatol. 2015;12:271–283.PubMedCrossRef
7.
Page MJ, Poritz LS, Tilberg AF, Zhang WJ, Chorney MJ, Koltun WA. Cd1d-restricted cellular lysis by peripheral blood lymphocytes: relevance to the inflammatory bowel diseases. J Surg Res. 2000;92:214–221.PubMedCrossRef
8.
Treiner E. Mucosal-associated invariant T cells in inflammatory bowel diseases: bystanders, defenders, or offenders? Front Immunol. 2015;6:27.PubMedPubMedCentral
9.
MacDonald TT. The role of activated T lymphocytes in gastrointestinal disease. Clin Exp Allergy. 1990;20:247–252.PubMedCrossRef
10.
Monteleone G, Biancone L, Marasco R, et al. Interleukin 12 is expressed and actively released by Crohn’s disease intestinal lamina propria mononuclear cells. Gastroenterology. 1997;112:1169–1178.PubMedCrossRef
11.
Monteleone G, Trapasso F, Parrello T, et al. Bioactive IL-18 expression is up-regulated in Crohn’s disease. J Immunol. 1999;163:143–147.PubMed
12.
Zorzi F, Monteleone I, Sarra M, et al. Distinct profiles of effector cytokines mark the different phases of Crohn’s disease. PLoS One. 2013;8:e54562.PubMedPubMedCentralCrossRef
13.
Fuss IJ, Neurath M, Boirivant M, et al. Disparate CD4+ lamina propria (LP) lymphokine secretion profiles in inflammatory bowel disease. Crohn’s disease LP cells manifest increased secretion of IFN-gamma, whereas ulcerative colitis LP cells manifest increased secretion of IL-5. J Immunol. 1996;157:1261–1270.PubMed
14.
Camoglio L, Te Velde AA, Tigges AJ, Das PK, Van Deventer SJ. Altered expression of interferon-gamma and interleukin-4 in inflammatory bowel disease. Inflamm Bowel Dis. 1998;4:285–290.PubMedCrossRef
15.
Heller F, Florian P, Bojarski C, 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.PubMedCrossRef
16.
Fuss IJ, Heller F, Boirivant M, et al. Nonclassical CD1d-restricted NK T cells that produce IL-13 characterize an atypical Th2 response in ulcerative colitis. J Clin Invest. 2004;113:1490–1497.PubMedPubMedCentralCrossRef
17.
Rovedatti L, Kudo T, Biancheri P, et al. Differential regulation of interleukin 17 and interferon gamma production in inflammatory bowel disease. Gut. 2009;58:1629–1636.PubMedCrossRef
18.
Biancheri P, Di Sabatino A, Ammoscato F, et al. Absence of a role for interleukin-13 in inflammatory bowel disease. Eur J Immunol. 2014;44:370–385.PubMedCrossRef
19.
Cepek KL, Parker CM, Madara JL, Brenner MB. Integrin alpha E beta 7 mediates adhesion of T lymphocytes to epithelial cells. J Immunol. 1993;150:3459–3470.PubMed
20.
Lamb CA, Mansfield JC, Tew GW, et al. αEβ7 integrin identifies subsets of Pro-inflammatory colonic CD4+ T lymphocytes in ulcerative colitis. J Crohns Colitis. 2017;11:610–620.PubMedCrossRef
21.
Gwela A, Siddhanathi P, Oxford IBD Cohort Investigators, et al. Th1 and innate lymphoid cells accumulate in primary sclerosing cholangitis-associated inflammatory bowel disease. J Crohns Colitis. 2017;11:1124–1134.PubMedPubMedCentralCrossRef
22.
Di Sabatino A, Rovedatti L, Kaur R, et al. Targeting gut T cell Ca2+ release-activated Ca2+ channels inhibits T cell cytokine production and T-box transcription factor T-bet in inflammatory bowel disease. J Immunol. 2009;183:3454–3462.PubMedCrossRef
23.
Boirivant M, Fuss IJ, Chu A, Strober W. Oxazolone colitis: a murine model of T helper cell type 2 colitis treatable with antibodies to interleukin 4. J Exp Med. 1998;188:1929–1939.PubMedPubMedCentralCrossRef
24.
Wilson MS, Ramalingam TR, Rivollier A, et al. Colitis and intestinal inflammation in IL10−/− mice results from IL-13Rα2-mediated attenuation of IL-13 activity. Gastroenterology. 2011;140:254–264.PubMedCrossRef
25.
Fichtner-Feigl S, Young CA, Kitani A, Geissler EK, Schlitt HJ, Strober W. IL-13 signaling via IL-13R alpha2 induces major downstream fibrogenic factors mediating fibrosis in chronic TNBS colitis. Gastroenterology. 2008;135:2003–2013.PubMedCrossRef
26.
Vainer B, Nielsen OH, Hendel J, Horn T, Kirman I. Colonic expression and synthesis of interleukin 13 and interleukin 15 in inflammatory bowel disease. Cytokine. 2000;12:1531–1536.PubMedCrossRef
27.
Kadivar K, Ruchelli ED, Markowitz JE, et al. Intestinal interleukin-13 in pediatric inflammatory bowel disease patients. Inflamm Bowel Dis. 2004;10:593–598.PubMedCrossRef
28.
Bernardo D, Vallejo-Díez S, Mann ER, et al. IL-6 promotes immune responses in human ulcerative colitis and induces a skin-homing phenotype in the dendritic cells and T cells they stimulate. Eur J Immunol. 2012;42:1337–1353.PubMedCrossRef
29.
Danese S, Rudziński J, Brandt W, et al. Tralokinumab for moderate-to-severe UC: a randomised, double-blind, placebo-controlled, phase IIa study. Gut. 2015;64:243–249.PubMedCrossRef
30.
Reinisch W, Panés J, Khurana S, et al. Anrukinzumab, an anti-interleukin 13 monoclonal antibody, in active UC: efficacy and safety from a phase IIa randomised multicentre study. Gut. 2015;64:894–900.PubMedCrossRef
31.
Veldhoen M, Uyttenhove C, van Snick J, et al. Transforming growth factor-beta ‘reprograms’ the differentiation of T helper 2 cells and promotes an interleukin 9-producing subset. Nat Immunol. 2008;9:1341–1346.PubMedCrossRef
32.
Dardalhon V, Awasthi A, Kwon H, et al. IL-4 inhibits TGF-beta-induced Foxp3+ T cells and together with TGF-beta, generates IL-9+ IL-10+ Foxp3(−) effector T cells. Nat Immunol. 2008;9:1347–1355.PubMedPubMedCentralCrossRef
33.
Gerlach K, McKenzie AN, Neurath MF, Weigmann B. IL-9 regulates intestinal barrier function in experimental T cell-mediated colitis. Tissue Barriers. 2015;3:e983777.PubMedPubMedCentralCrossRef
34.
Gerlach K, Hwang Y, Nikolaev A, et al. TH9 cells that express the transcription factor PU.1 drive T cell-mediated colitis via IL-9 receptor signaling in intestinal epithelial cells. Nat Immunol. 2014;15:676–686.PubMedCrossRef
35.
Nalleweg N, Chiriac MT, Podstawa E, et al. IL-9 and its receptor are predominantly involved in the pathogenesis of UC. Gut. 2015;64:743–755.PubMedCrossRef
36.
37.
Seidelin JB, Bjerrum JT, Coskun M, Widjaya B, Vainer B, Nielsen OH. IL-33 is upregulated in colonocytes of ulcerative colitis. Immunol Lett. 2010;128:80–85.PubMedCrossRef
38.
Pastorelli L, Garg RR, Hoang SB, et al. Epithelial-derived IL-33 and its receptor ST2 are dysregulated in ulcerative colitis and in experimental Th1/Th2 driven enteritis. Proc Natl Acad Sci USA. 2010;107:8017–8022.PubMedPubMedCentralCrossRef
39.
Volpe E, Servant N, Zollinger R, et al. A critical function for transforming growth factor-beta, interleukin 23 and proinflammatory cytokines in driving and modulating human T(H)-17 responses. Nat Immunol. 2008;9:650–657.PubMedCrossRef
40.
41.
Sugihara T, Kobori A, Imaeda H, et al. The increased mucosal mRNA expressions of complement C3 and interleukin-17 in inflammatory bowel disease. Clin Exp Immunol. 2010;160:386–393.PubMedPubMedCentralCrossRef
42.
Monteleone G, Monteleone I, Fina D, et al. Interleukin-21 enhances T-helper cell type I signaling and interferon-gamma production in Crohn’s disease. Gastroenterology. 2005;128:687–694.PubMedCrossRef
43.
Fina D, Sarra M, Fantini MC, et al. Regulation of gut inflammation and th17 cell response by interleukin-21. Gastroenterology. 2008;134:1038–1048.PubMedCrossRef
44.
Harrington LE, Hatton RD, Mangan PR, et al. Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol. 2005;6:1123–1132.PubMedCrossRef
45.
46.
Biancheri P, Pender SL, Ammoscato F, et al. The role of interleukin 17 in Crohn’s disease-associated intestinal fibrosis. Fibrogenes Tissue Repair. 2013;6:13.CrossRef
47.
Kobayashi T, Okamoto S, Hisamatsu T, et al. IL23 differentially regulates the Th1/Th17 balance in ulcerative colitis and Crohn’s disease. Gut. 2008;57:1682–1689.PubMedCrossRef
48.
O’Garra A, Vieira P. Regulatory T cells and mechanisms of immune system control. Nat Med. 2004;10:801–805.PubMedCrossRef
49.
Izcue A, Coombes JL, Powrie F. Regulatory lymphocytes and intestinal inflammation. Annu Rev Immunol. 2009;27:313–338.PubMedCrossRef
50.
Fantini MC, Becker C, Monteleone G, Pallone F, Galle PR, Neurath MF. Cutting edge: TGF-beta induces a regulatory phenotype in CD4 + CD25-T cells through Foxp3 induction and down-regulation of Smad7. J Immunol. 2004;172:5149–5153.PubMedCrossRef
51.
Dominitzki S, Fantini MC, Neufert C, et al. Cutting edge: trans-signaling via the soluble IL-6R abrogates the induction of FoxP3 in naive CD4 + CD25 T cells. J Immunol. 2007;179:2041–2045.PubMedCrossRef
52.
Maul J, Loddenkemper C, Mundt P, et al. Peripheral and intestinal regulatory CD4 + CD25(high) T cells in inflammatory bowel disease. Gastroenterology. 2005;128:1868–1878.PubMedCrossRef
53.
Chamouard P, Monneaux F, Richert Z, et al. Diminution of circulating CD4 + CD25 high T cells in naïve Crohn’s disease. Dig Dis Sci. 2009;54:2084–2093.PubMedCrossRef
54.
Li Z, Vermeire S, Bullens D, et al. Restoration of Foxp3+ regulatory T-cell subsets and Foxp3− type 1 regulatory-like T cells in inflammatory bowel diseases during anti-tumor necrosis factor therapy. Inflamm Bowel Dis. 2015;21:2418–2428.PubMed
55.
Saruta M, Yu QT, Fleshner PR, et al. Characterization of FOXP3 + CD4+ regulatory T cells in Crohn’s disease. Clin Immunol. 2007;125:281–290.PubMedCrossRef
56.
Fahlén L, Read S, Gorelik L, et al. T cells that cannot respond to TGF-beta escape control by CD4(+)CD25(+) regulatory T cells. J Exp Med. 2005;201:737–746.PubMedPubMedCentralCrossRef
57.
Monteleone G, Kumberova A, Croft NM, McKenzie C, Steer HW, MacDonald TT. Blocking Smad7 restores TGF-beta1 signaling in chronic inflammatory bowel disease. J Clin Invest. 2001;108:601–609.PubMedPubMedCentralCrossRef
58.
Biancheri P, Giuffrida P, Docena GH, MacDonald TT, Corazza GR, Di Sabatino A. The role of transforming growth factor (TGF)-β in modulating the immune response and fibrogenesis in the gut. Cytokine Growth Factor Rev. 2014;25:45–55.PubMedCrossRef
59.
Fantini MC, Rizzo A, Fina D, et al. Smad7 controls resistance of colitogenic T cells to regulatory T cell-mediated suppression. Gastroenterology. 2009;136:1308–1316.PubMedCrossRef
60.
Le Bourhis L, Guerri L, Dusseaux M, Martin E, Soudais C, Lantz O. Mucosal-associated invariant T cells: unconventional development and function. Trends Immunol. 2011;32:212–218.PubMedCrossRef
61.
Ruijing X, Mengjun W, Xiaoling Z, et al. Jα33+ MAIT cells play a protective role in TNBS induced intestinal inflammation. Hepatogastroenterology. 2012;59:762–767.PubMed
62.
Serriari NE, Eoche M, Lamotte L, et al. Innate mucosal-associated invariant T (MAIT) cells are activated in inflammatory bowel diseases. Clin Exp Immunol. 2014;176:266–274.PubMedPubMedCentralCrossRef
63.
Haga K, Chiba A, Shibuya T, et al. MAIT cells are activated and accumulated in the inflamed mucosa of ulcerative colitis. J Gastroenterol Hepatol. 2016;31:965–972.PubMedCrossRef
64.
Tominaga K, Yamagiwa S, Setsu T, et al. Possible involvement of mucosal-associated invariant T cells in the progression of inflammatory bowel diseases. Biomed Res. 2017;38:111–121.PubMedCrossRef
65.
Hiejima E, Kawai T, Nakase H, et al. Reduced Numbers and proapoptotic features of mucosal-associated invariant T cells as a characteristic finding in patients with inflammatory bowel disease. Inflamm Bowel Dis. 2015;21:1529–1540.PubMedCrossRef
66.
Saubermann LJ, Beck P, De Jong YP, et al. Activation of natural killer T cells by alpha-galactosylceramide in the presence of CD1d provides protection against colitis in mice. Gastroenterology. 2000;119:119–128.PubMedCrossRef
67.
Numata Y, Tazuma S, Ueno Y, Nishioka T, Hyogo H, Chayama K. Therapeutic effect of repeated natural killer T cell stimulation in mouse cholangitis complicated by colitis. Dig Dis Sci. 2005;50:1844–1851.PubMedCrossRef
68.
Ueno Y, Tanaka S, Sumii M, et al. Single dose of OCH improves mucosal T helper type 1/T helper type 2 cytokine balance and prevents experimental colitis in the presence of v alpha 14 natural killer T cells in mice. Inflamm Bowel Dis. 2005;11:35–41.PubMedCrossRef
69.
Hornung M, Farkas SA, Sattler C, Schlitt HJ, Geissler EK. DX5+ NKT cells induce the death of colitis-associated cells: involvement of programmed death ligand-1. Eur J Immunol. 2006;36:1210–1221.PubMedCrossRef
70.
Shibolet O, Alper R, Zolotarov L, et al. The role of intrahepatic CD8+ T cell trapping and NK1.1+ cells in liver-mediated immune regulation. Clin Immunol. 2004;111:82–92.PubMedCrossRef
71.
Shibolet O, Kalish Y, Klein A, et al. Adoptive transfer of ex vivo immune programmed NKT lymphocytes alleviates immune-mediated colitis. J Leukoc Biol. 2004;75:76–86.PubMedCrossRef
72.
Heller F, Fuss IJ, Nieuwenhuis EE, Blumberg RS, Strober W. Oxazolone colitis, a Th2 colitis model resembling ulcerative colitis, is mediated by IL-13-producing NK-T cells. Immunity. 2002;17:629–638.PubMedCrossRef
73.
Perera L, Shao L, Patel A, et al. Expression of nonclassical class I molecules by intestinal epithelial cells. Inflamm Bowel Dis. 2007;13:298–307.PubMedCrossRef
74.
Grose RH, Thompson FM, Baxter AG, Pellicci DG, Cummins AG. Deficiency of invariant NK T cells in Crohn’s disease and ulcerative colitis. Dig Dis Sci. 2007;52:1415–1422.PubMedCrossRef
75.
Fuss IJ, Joshi B, Yang Z, et al. IL-13Rα2-bearing, type II NKT cells reactive to sulfatide self-antigen populate the mucosa of ulcerative colitis. Gut. 2014;63:1728–1736.PubMedPubMedCentralCrossRef
76.
Fuchs A, Vermi W, Lee JS, et al. Intraepithelial type 1 innate lymphoid cells are a unique subset of IL-12- and IL-15-responsive IFN-γ-producing cells. Immunity. 2013;38:769–781.PubMedPubMedCentralCrossRef
77.
Buonocore S, Ahern PP, Uhlig HH, et al. Innate lymphoid cells drive interleukin-23-dependent innate intestinal pathology. Nature. 2010;464:1371–1375.PubMedPubMedCentralCrossRef
78.
Powell N, Walker AW, Stolarczyk E, et al. The transcription factor T-bet regulates intestinal inflammation mediated by interleukin-7 receptor + innate lymphoid cells. Immunity. 2012;37:674–684.PubMedPubMedCentralCrossRef
79.
Geremia A, Arancibia-Cárcamo CV, Fleming MP, et al. IL-23-responsive innate lymphoid cells are increased in inflammatory bowel disease. J Exp Med. 2011;208:1127–1133.PubMedPubMedCentralCrossRef
80.
Powell N, Lo JW, Biancheri P, et al. Interleukin 6 increases production of cytokines by colonic innate lymphoid cells in mice and patients with chronic intestinal inflammation. Gastroenterology. 2015;149:456–467.PubMedPubMedCentralCrossRef
81.
Bernink JH, Peters CP, Munneke M, et al. Human type 1 innate lymphoid cells accumulate in inflamed mucosal tissues. Nat Immunol. 2013;14:221–229.PubMedCrossRef
82.
Satoh-Takayama N, Vosshenrich CA, Lesjean-Pottier S, et al. Microbial flora drives interleukin 22 production in intestinal NKp46+ cells that provide innate mucosal immune defense. Immunity. 2008;29:958–970.PubMedCrossRef
83.
Bernink JH, Krabbendam L, Germar K, et al. Interleukin-12 and -23 control plasticity of CD127(+) group 1 and group 3 innate lymphoid cells in the intestinal lamina propria. Immunity. 2015;43:146–160.PubMedCrossRef
84.
85.
Oka A, Ishihara S, Mishima Y, et al. Role of regulatory B cells in chronic intestinal inflammation: association with pathogenesis of Crohn’s disease. Inflamm Bowel Dis. 2014;20:315–328.PubMedCrossRef
86.
Ansary MM, Ishihara S, Oka A, et al. Apoptotic cells ameliorate chronic intestinal inflammation by enhancing regulatory B-cell function. Inflamm Bowel Dis. 2014;20:2308–2320.PubMedCrossRef
87.
Li Z, Vermeire S, Bullens D, et al. Anti-tumor necrosis factor therapy restores peripheral blood B-cell subsets and CD40 Expression in inflammatory bowel diseases. Inflamm Bowel Dis. 2015;21:2787–2796.PubMedCrossRef
88.
Di Sabatino A, Rosado MM, Cazzola P, et al. Splenic function and IgM-memory B cells in Crohn’s disease patients treated with infliximab. Inflamm Bowel Dis. 2008;14:591–596.PubMedCrossRef
89.
Keren DF, Appelman HD, Dobbins WO 3rd, et al. Correlation of histopathologic evidence of disease activity with the presence of immunoglobulin-containing cells in the colons of patients with inflammatory bowel disease. Hum Pathol. 1984;15:757–763.PubMedCrossRef
90.
Giuffrida P, Pinzani M, Corazza GR, Di Sabatino A. Biomarkers of intestinal fibrosis—one step towards clinical trials for stricturing inflammatory bowel disease. United European Gastroenterol J. 2016;4:523–530.PubMedPubMedCentralCrossRef
91.
Uo M, Hisamatsu T, Miyoshi J, et al. Mucosal CXCR4+ IgG plasma cells contribute to the pathogenesis of human ulcerative colitis through FcγR-mediated CD14 macrophage activation. Gut. 2013;62:1734–1744.PubMedCrossRef
92.
Halstensen TS, Mollnes TE, Garred P, Fausa O, Brandtzaeg P. Epithelial deposition of immunoglobulin G1 and activated complement (C3b and terminal complement complex) in ulcerative colitis. Gastroenterology. 1990;98:1264–1271.PubMedCrossRef
93.
Gordon JN, Pickard KM, Di Sabatino A, et al. Matrix metalloproteinase-3 production by gut IgG plasma cells in chronic inflammatory bowel disease. Inflamm Bowel Dis. 2008;14:195–203.PubMedCrossRef
94.
Giuffrida P, Biancheri P, MacDonald TT. Proteases and small intestinal barrier function in health and disease. Curr Opin Gastroenterol. 2014;30:147–153.PubMedCrossRef
95.
Cupi ML, Sarra M, Marafini I, et al. Plasma cells in the mucosa of patients with inflammatory bowel disease produce granzyme B and possess cytotoxic activities. J Immunol. 2014;192:6083–6091.PubMedCrossRef
96.
97.
Wang Z, Wang Z, Wang J, Diao Y, Qian X, Zhu N. T-bet-expressing B cells are positively associated with Crohn’s disease activity and support Th1 inflammation. DNA Cell Biol. 2016;35:628–635.PubMedCrossRef
98.
Sandborn WJ, Cyrille M, Hansen MB, et al. Efficacy and safety of abrilumab in subjects with moderate to severe ulcerative colitis: results of a phase 2b, randomised, double-blind, multiple-dose, placebo-controlled study. Gastroenterology. 2017;152:S198.CrossRef
99.
Sandborn WJ, Cyrille M, Hansen MB, et al. Efficacy and safety of abrilumab (AMG 181/MEDI 7183) therapy for moderate to severe Crohn’s disease. Gastroenterology. 2017;152:S598.
100.
Vermeire S, O’Byrne S, Keir M, et al. Etrolizumab as induction therapy for ulcerative colitis: a randomised, controlled, phase 2 trial. Lancet. 2014;384:309–318.PubMedCrossRef
101.
Vermeire S, Sandborn WJ, Danese S, et al. Anti-MAdCAM antibody (PF-00547659) for ulcerative colitis (TURANDOT): a phase 2, randomised, double-blind, placebo-controlled trial. Lancet. 2017;390:135–144.PubMedCrossRef
102.
Sandborn WJ, Lee SD, Tarabar D et al. Phase II evaluation of anti-MAdCAM antibody PF-00547659 in the treatment of Crohn’s disease: report of the OPERA study. Gut. 10/5/2017 [Epub ahead of print].
103.
Schreiber S, Nikolaus S, Malchow H, et al. Absence of efficacy of subcutaneous antisense ICAM-1 treatment of chronic active Crohn’s disease. Gastroenterology. 2001;120:1339–1346.PubMedCrossRef
104.
Miner PB Jr, Wedel MK, Xia S, Baker BF. Safety and efficacy of two dose formulations of alicaforsen enema compared with mesalazine enema for treatment of mild to moderate left-sided ulcerative colitis: a randomized, double-blind, active-controlled trial. Aliment Pharmacol Ther. 2006;23:1403–1413.PubMedCrossRef
105.
Leiper K, Martin K, Ellis A, et al. Randomised placebo-controlled trial of rituximab (anti-CD20) in active ulcerative colitis. Gut. 2011;60:1520–1526.PubMedCrossRef
106.
Sandborn WJ, Colombel JF, Frankel M, et al. Anti-CD3 antibody visilizumab is not effective in patients with intravenous corticosteroid-refractory ulcerative colitis. Gut. 2010;59:1485–1492.PubMedCrossRef
107.
van der Woude CJ, Stokkers P, van Bodegraven AA, et al. Phase I, double-blind, randomized, placebo-controlled, dose-escalation study of NI-0401 (a fully human anti-CD3 monoclonal antibody) in patients with moderate to severe active Crohn’s disease. Inflamm Bowel Dis. 2010;16:1708–1716.PubMedCrossRef
108.
Vossenkämper A, Hundsrucker C, Page K, et al. A CD3-specific antibody reduces cytokine production and alters phosphoprotein profiles in intestinal tissues from patients with inflammatory bowel disease. Gastroenterolog.. 2014;147:172–183.CrossRef
109.
Creed TJ, Probert CS, Norman MN, et al. Basiliximab for the treatment of steroid-resistant ulcerative colitis: further experience in moderate and severe disease. Aliment Pharmacol Ther. 2006;23:1435–1442.PubMedCrossRef
110.
Sands BE, Sandborn WJ, Creed TJ, et al. Basiliximab does not increase efficacy of corticosteroids in patients with steroid-refractory ulcerative colitis. Gastroenterology. 2012;143:356–364.PubMedCrossRef
111.
Van Assche G, Sandborn WJ, Feagan BG, et al. Daclizumab, a humanised monoclonal antibody to the interleukin 2 receptor (CD25), for the treatment of moderately to severely active ulcerative colitis: a randomised, double blind, placebo controlled, dose ranging trial. Gut. 2006;55:1568–1574.PubMedPubMedCentralCrossRef
112.
Allez M, Skolnick BE, Wisniewska-Jarosinska M, Petryka R, Overgaard RV. Anti-NKG2D monoclonal antibody (NNC0142-0002) in active Crohn’s disease: a randomised controlled trial. Gut. 2017;66:1918–1925.PubMedCrossRef
113.
Reinisch W, de Villiers W, Bene L, et al. Fontolizumab in moderate to severe Crohn’s disease: a phase 2, randomized, double-blind, placebo-controlled, multiple-dose study. Inflamm Bowel Dis. 2010;16:233–242.PubMedCrossRef
114.
Hueber W, Sands BE, Lewitzky S, et al. Secukinumab, a human anti-IL-17A monoclonal antibody, for moderate to severe Crohn’s disease: unexpected results of a randomised, double-blind placebo-controlled trial. Gut. 2012;61:1693–1700.PubMedPubMedCentralCrossRef
115.
Feagan BG, Sandborn WJ, Gasink C, et al. Ustekinumab as induction and maintenance therapy for Crohn’s disease. N Engl J Med. 2016;375:1946–1960.PubMedCrossRef
116.
117.
Meeran SM, Katiyar S, Elmets CA, Katiyar SK. Interleukin-12 deficiency is permissive for angiogenesis in UV radiation-induced skin tumors. Cancer Res. 2007;67:3785–3793.PubMedPubMedCentralCrossRef
118.
Sands BE, Chen J, Feagan BG, et al. Efficacy and safety of MEDI2070, an antibody against interleukin 23, in patients with moderate to severe Crohn’s disease: a phase 2a study. Gastroenterology. 2017;153:77–86.PubMedCrossRef
119.
Feagan BG, Sandborn WJ, D’Haens G, et al. Induction therapy with the selective interleukin-23 inhibitor risankizumab in patients with moderate-to-severe Crohn’s disease: a randomised, double-blind, placebo-controlled phase 2 study. Lancet. 2017;389:1699–1709.PubMedCrossRef
120.
121.
122.
Ito H, Takazoe M, Fukuda Y, et al. A pilot randomized trial of a human anti-interleukin-6 receptor monoclonal antibody in active Crohn’s disease. Gastroenterology. 2004;126:989–996.PubMedCrossRef
123.
Sandborn WJ, Su C, Sands BE, et al. Tofacitinib as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2017;376:1723–1736.PubMedCrossRef
124.
Panés J, Sandborn WJ, Schreiber S, et al. Tofacitinib for induction and maintenance therapy of Crohn’s disease: results of two phase IIb randomized placebo-controlled trials. Gut. 2017;66:1049–1059.PubMedPubMedCentralCrossRef
125.
Vermeire S, Schreiber S, Petryka R, et al. Clinical remission in patients with moderate-to-severe Crohn’s disease treated with filgotinib (the FITZROY study): results from a phase 2, double-blind, randomised, placebo-controlled trial. Lancet. 2017;389:266–275.PubMedCrossRef
126.
127.
Popp V, Gerlach K, Mott S, et al. Rectal delivery of a DNAzyme that specifically blocks the transcription factor GATA3 and reduces colitis in mice. Gastroenterology. 2017;152:176–192.PubMedCrossRef
128.
Colombel JF, Rutgeerts P, Malchow H, et al. Interleukin 10 (Tenovil) in the prevention of postoperative recurrence of Crohn’s disease. Gut. 2001;49:42–46.PubMedPubMedCentralCrossRef
129.
Schreiber S, Fedorak RN, Nielsen OH, et al. Safety and efficacy of recombinant human interleukin 10 in chronic active Crohn’s disease. Crohn’s disease IL-10 Cooperative Study Group. Gastroenterology. 2000;119:1461–1472.PubMedCrossRef
130.
Fedorak RN, Gangl A, Elson CO, et al. Recombinant human interleukin 10 in the treatment of patients with mild to moderately active Crohn’s disease. The interleukin 10 Inflammatory Bowel Disease Cooperative Study Group. Gastroenterology. 2000;119:1473–1482.PubMedCrossRef
131.
Monteleone G, Neurath MF, Ardizzone S, et al. Mongersen, an oral SMAD7 antisense oligonucleotide, and Crohn’s disease. N Engl J Med. 2015;372:1104–1113.PubMedCrossRef
132.
Monteleone G, Di Sabatino A, Ardizzone S, et al. Impact of patient characteristics on the clinical efficacy of mongersen (GED-0301), an oral Smad7 antisense oligonucleotide, in active Crohn’s disease. Aliment Pharmacol Ther. 2016;43:717–724.PubMedPubMedCentralCrossRef
Metadata
Title
Old and New Lymphocyte Players in Inflammatory Bowel Disease
Authors
Paolo Giuffrida
Gino Roberto Corazza
Antonio Di Sabatino
Publication date
01-02-2018
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 2/2018
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-017-4892-4

Other articles of this Issue 2/2018

Digestive Diseases and Sciences 2/2018 Go to the issue

Correspondence

Pursuing a Medical Career Outside of the USA

Original Article

Distinct Expression of Phenotypic Markers in Placodes- and Neural Crest-Derived Afferent Neurons Innervating the Rat Stomach

Original Article

Proton Pump Inhibitors Independently Protect Against Early Allograft Injury or Chronic Rejection After Lung Transplantation

Original Article

Endoscopic Therapy of Biliary Injury After Cholecystectomy

Original Article

Improving the Quality of Inpatient Bowel Preparation for Colonoscopies

Original Article

SX-Ella Stent Danis Effectively Controls Refractory Variceal Bleed in Patients with Acute-on-Chronic Liver Failure
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Heart Failure Video

Year in Review: Heart failure and cardiomyopathies

Watch now

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits