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Published in: BMC Immunology 1/2010

Open Access 01-12-2010 | Research article

Differential mucosal expression of Th17-related genes between the inflamed colon and ileum of patients with inflammatory bowel disease

Authors: Sara Bogaert, Debby Laukens, Harald Peeters, Lode Melis, Kim Olievier, Nico Boon, Gust Verbruggen, Jo Vandesompele, Dirk Elewaut, Martine De Vos

Published in: BMC Immunology | Issue 1/2010

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Abstract

Background

Immunological and genetic findings implicate Th17 effector cytokines in the pathogenesis of inflammatory bowel disease (IBD). Expression of Th17 pathway-associated genes is mainly studied in colonic disease. The present study assessed the mRNA expression levels of Th17 effector cytokines (IL17A, IL17F, IL21, IL22 and IL26) and genes involved in differentiation (IL6, IL1B, TGFB1, IL23A and STAT3) and recruitment of Th17 cells (CCR6 and CCL20) by quantitative real-time PCR analysis of colonic and ileal biopsies from 22 healthy control subjects, 26 patients with Crohn's disease (CD) and 12 patients with ulcerative colitis (UC). Inflammation was quantified by measuring expression of the inflammatory mediators IL8 and TNF.

Results

Evaluation of mRNA expression levels in colonic and ileal control samples revealed that TNF, TGFB1, STAT3 and CCR6 were expressed at higher levels in the ileum than in the colon. Expression of all the Th17 pathway-associated genes was increased in inflamed colonic samples. The increased expression of these genes was predominantly observed in samples from UC patients and was associated with more intense inflammation. Although increased expression of IL17A, IL17F, IL21 and IL26 was detected in inflamed ileal samples, expression of the indispensable Th17 cell differentiation factors TGFB1 and IL23A, the signaling molecule STAT3 and the Th17 recruitment factors CCR6 and CCL20 were unchanged.

Conclusions

Our findings suggest that immune regulation is different in colonic and ileal disease, which might have important consequences for therapeutic intervention.
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Literature
1.
go back to reference Darfeuille-Michaud A, Neut C, Barnich N, Lederman E, Di Martino P, Desreumaux P, Gambiez L, Joly B, Cortot A, Colombel JF: Presence of adherent Escherichia coli strains in ileal mucosa of patients with Crohn's disease. Gastroenterol. 1998, 115: 1405-1413. 10.1016/S0016-5085(98)70019-8.CrossRef Darfeuille-Michaud A, Neut C, Barnich N, Lederman E, Di Martino P, Desreumaux P, Gambiez L, Joly B, Cortot A, Colombel JF: Presence of adherent Escherichia coli strains in ileal mucosa of patients with Crohn's disease. Gastroenterol. 1998, 115: 1405-1413. 10.1016/S0016-5085(98)70019-8.CrossRef
2.
go back to reference Kotlowski R, Bernstein CN, Sepehri S, Krause DO: High prevalence of Escherichia coli belonging to the B2+D phylogenetic group in inflammatory bowel disease. Gut. 2007, 56: 669-675. 10.1136/gut.2006.099796.PubMedCentralCrossRefPubMed Kotlowski R, Bernstein CN, Sepehri S, Krause DO: High prevalence of Escherichia coli belonging to the B2+D phylogenetic group in inflammatory bowel disease. Gut. 2007, 56: 669-675. 10.1136/gut.2006.099796.PubMedCentralCrossRefPubMed
3.
4.
go back to reference 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. 10.1136/gut.2008.163667.CrossRefPubMed 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. 10.1136/gut.2008.163667.CrossRefPubMed
5.
go back to reference Yen D, Cheung J, Scheerens H, Poulet F, McClanahan T, McKenzie B, Kleinschek MA, Owyang A, Mattson J, Blumenschein W, Murphy E, Sathe M, Cua DJ, Kastelein RA, Rennick D: IL-23 is essential for T cell-mediated colitis and promotes inflammation via IL-17 and IL-6. J Clin Invest. 2006, 116: 1310-1316. 10.1172/JCI21404.PubMedCentralCrossRefPubMed Yen D, Cheung J, Scheerens H, Poulet F, McClanahan T, McKenzie B, Kleinschek MA, Owyang A, Mattson J, Blumenschein W, Murphy E, Sathe M, Cua DJ, Kastelein RA, Rennick D: IL-23 is essential for T cell-mediated colitis and promotes inflammation via IL-17 and IL-6. J Clin Invest. 2006, 116: 1310-1316. 10.1172/JCI21404.PubMedCentralCrossRefPubMed
6.
go back to reference Parronchi P, Romagnani P, Annunziato F, Sampognaro S, Becchio A, Giannarini L, Maggi E, Pupilli C, Tonelli F, Romagnani S: Type 1 T-helper cell predominance and interleukin-12 expression in the gut of patients with Crohn's disease. Am J Pathol. 1997, 150: 823-832.PubMedCentralPubMed Parronchi P, Romagnani P, Annunziato F, Sampognaro S, Becchio A, Giannarini L, Maggi E, Pupilli C, Tonelli F, Romagnani S: Type 1 T-helper cell predominance and interleukin-12 expression in the gut of patients with Crohn's disease. Am J Pathol. 1997, 150: 823-832.PubMedCentralPubMed
7.
go back to reference Hue S, Ahern P, Buonocore S, Kullberg MC, Cua DJ, McKenzie BS, Powrie F, Maloy KJ: Interleukin-23 drives innate and T cell-mediated intestinal inflammation. J Exp Med. 2006, 203: 2473-2483. 10.1084/jem.20061099.PubMedCentralCrossRefPubMed Hue S, Ahern P, Buonocore S, Kullberg MC, Cua DJ, McKenzie BS, Powrie F, Maloy KJ: Interleukin-23 drives innate and T cell-mediated intestinal inflammation. J Exp Med. 2006, 203: 2473-2483. 10.1084/jem.20061099.PubMedCentralCrossRefPubMed
8.
go back to reference Hue S, Maloy K, McKensie B, Cua D, Powrie F: IL-23 and not IL-12 is essential for the development of IBD. Inflamm Bowel Dis. 2006, 12: S25-10.1097/00054725-200604002-00059.CrossRef Hue S, Maloy K, McKensie B, Cua D, Powrie F: IL-23 and not IL-12 is essential for the development of IBD. Inflamm Bowel Dis. 2006, 12: S25-10.1097/00054725-200604002-00059.CrossRef
9.
go back to reference Heller F, Florian P, Bojarski C, Richter J, Christ M, Hillenbrand B, Mankertz J, Gitter AH, Burgel N, Fromm M, Zeitz M, Fuss I, Strober W, Schulzke JD: Interleukin-13 is the key effector Th2 cytokine in ulcerative colitis that affects epithelial tight junctions, apoptosis, and cell restitution. Gastroenterol. 2005, 129: 550-564.CrossRef Heller F, Florian P, Bojarski C, Richter J, Christ M, Hillenbrand B, Mankertz J, Gitter AH, Burgel N, Fromm M, Zeitz M, Fuss I, Strober W, Schulzke JD: Interleukin-13 is the key effector Th2 cytokine in ulcerative colitis that affects epithelial tight junctions, apoptosis, and cell restitution. Gastroenterol. 2005, 129: 550-564.CrossRef
10.
go back to reference Wilson NJ, Boniface K, Chan JR, McKenzie BS, Blumenschein WM, Mattson JD, Basham B, Smith K, Chen T, Morel F, Lecron JC, Kastelein RA, Cua DJ, McClanahan TK, Bowman EP, Malefyt RD: Development, cytokine profile and function of human interleukin 17-producing helper T cells. Nat Immunol. 2007, 8: 950-957. 10.1038/ni1497.CrossRefPubMed Wilson NJ, Boniface K, Chan JR, McKenzie BS, Blumenschein WM, Mattson JD, Basham B, Smith K, Chen T, Morel F, Lecron JC, Kastelein RA, Cua DJ, McClanahan TK, Bowman EP, Malefyt RD: Development, cytokine profile and function of human interleukin 17-producing helper T cells. Nat Immunol. 2007, 8: 950-957. 10.1038/ni1497.CrossRefPubMed
11.
go back to reference Wolk K, Kunz S, Witte E, Friedrich M, Asadullah K, Sabat R: IL-22 increases the innate immunity of tissues. Immunity. 2004, 21: 241-254. 10.1016/j.immuni.2004.07.007.CrossRefPubMed Wolk K, Kunz S, Witte E, Friedrich M, Asadullah K, Sabat R: IL-22 increases the innate immunity of tissues. Immunity. 2004, 21: 241-254. 10.1016/j.immuni.2004.07.007.CrossRefPubMed
12.
go back to reference Liang SC, Tan XY, Luxenberg DP, Karim R, Dunussi-Joannopoulos K, Collins M, Fouser LA: Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides. J Exp Med. 2006, 203: 2271-2279. 10.1084/jem.20061308.PubMedCentralCrossRefPubMed Liang SC, Tan XY, Luxenberg DP, Karim R, Dunussi-Joannopoulos K, Collins M, Fouser LA: Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides. J Exp Med. 2006, 203: 2271-2279. 10.1084/jem.20061308.PubMedCentralCrossRefPubMed
13.
go back to reference Kinugasa T, Sakaguchi T, Gu XB, Reinecker HC: Claudins regulate the intestinal barrier in response to immune mediators. Gastroenterol. 2000, 118: 1001-1011. 10.1016/S0016-5085(00)70351-9.CrossRef Kinugasa T, Sakaguchi T, Gu XB, Reinecker HC: Claudins regulate the intestinal barrier in response to immune mediators. Gastroenterol. 2000, 118: 1001-1011. 10.1016/S0016-5085(00)70351-9.CrossRef
14.
go back to reference Brand S, Beigel F, Olszak T, Zitzmann K, Eichhorst ST, Otte JM, Diepolder H, Marquardt A, Jagla W, Popp A, Leclair S, Herrmann K, Seiderer J, Ochsenkuhn T, Goke B, Auernhammer CJ, Dambacher J: IL-22 is increased in active Crohn's disease and promotes proinflammatory gene expression and intestinal epithelial cell migration. Am J Physiol Gastrointest Liver Physiol. 2006, 290: G827-G838. 10.1152/ajpgi.00513.2005.CrossRefPubMed Brand S, Beigel F, Olszak T, Zitzmann K, Eichhorst ST, Otte JM, Diepolder H, Marquardt A, Jagla W, Popp A, Leclair S, Herrmann K, Seiderer J, Ochsenkuhn T, Goke B, Auernhammer CJ, Dambacher J: IL-22 is increased in active Crohn's disease and promotes proinflammatory gene expression and intestinal epithelial cell migration. Am J Physiol Gastrointest Liver Physiol. 2006, 290: G827-G838. 10.1152/ajpgi.00513.2005.CrossRefPubMed
15.
go back to reference Yang XO, Pappu BP, Nurieva R, Akimzhanov A, Kang HS, Chung Y, Ma L, Shah B, Panopoulos AD, Schluns KS, Watowich SS, Tian Q, Jetten AM, Dong C: T helper 17 lineage differentiation is programmed by orphan nuclear receptors ROR alpha and ROR gamma. Immunity. 2008, 28: 29-39. 10.1016/j.immuni.2007.11.016.PubMedCentralCrossRefPubMed Yang XO, Pappu BP, Nurieva R, Akimzhanov A, Kang HS, Chung Y, Ma L, Shah B, Panopoulos AD, Schluns KS, Watowich SS, Tian Q, Jetten AM, Dong C: T helper 17 lineage differentiation is programmed by orphan nuclear receptors ROR alpha and ROR gamma. Immunity. 2008, 28: 29-39. 10.1016/j.immuni.2007.11.016.PubMedCentralCrossRefPubMed
16.
go back to reference Yang L, Anderson DE, Baecher-Allan C, Hastings WD, Bettelli E, Oukka M, Kuchroo VK, Hafler DA: IL-21 and TGF-beta are required for differentiation of human T(H)17 cells. Nature. 2008, 454: 350-U55. 10.1038/nature07021.PubMedCentralCrossRefPubMed Yang L, Anderson DE, Baecher-Allan C, Hastings WD, Bettelli E, Oukka M, Kuchroo VK, Hafler DA: IL-21 and TGF-beta are required for differentiation of human T(H)17 cells. Nature. 2008, 454: 350-U55. 10.1038/nature07021.PubMedCentralCrossRefPubMed
17.
go back to reference Pene J, Chevalier S, Preisser L, Venereau E, Guilleux MH, Ghannam S, Moles JP, Danger Y, Ravon E, Lesaux S, Yssel H, Gascan H: Chronically inflamed human tissues are infiltrated by highly differentiated Th17 lymphocytes. J Immunol. 2008, 180: 7423-7430.CrossRefPubMed Pene J, Chevalier S, Preisser L, Venereau E, Guilleux MH, Ghannam S, Moles JP, Danger Y, Ravon E, Lesaux S, Yssel H, Gascan H: Chronically inflamed human tissues are infiltrated by highly differentiated Th17 lymphocytes. J Immunol. 2008, 180: 7423-7430.CrossRefPubMed
18.
go back to reference Manel N, Unutmaz D, Littman DR: The differentiation of human T(H)-17 cells requires transforming growth factor-beta and induction of the nuclear receptor ROR gammat. Nat Immunol. 2008, 9: 641-649. 10.1038/ni.1610.PubMedCentralCrossRefPubMed Manel N, Unutmaz D, Littman DR: The differentiation of human T(H)-17 cells requires transforming growth factor-beta and induction of the nuclear receptor ROR gammat. Nat Immunol. 2008, 9: 641-649. 10.1038/ni.1610.PubMedCentralCrossRefPubMed
19.
go back to reference Ivanov II, McKenzie BS, Zhou L, Tadokoro CE, Lepelley A, Lafaille JJ, Cua DJ, Littman DR: The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell. 2006, 126: 1121-1133. 10.1016/j.cell.2006.07.035.CrossRefPubMed Ivanov II, McKenzie BS, Zhou L, Tadokoro CE, Lepelley A, Lafaille JJ, Cua DJ, Littman DR: The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell. 2006, 126: 1121-1133. 10.1016/j.cell.2006.07.035.CrossRefPubMed
20.
go back to reference Annunziato F, Cosmi L, Santarlasci V, Maggi L, Liotta F, Mazzinghi B, Parente E, Fili L, Ferri S, Frosali F, Giudici F, Romagnani P, Parronchi P, Tonelli F, Maggi E: Phenotypic and functional features of human Th17 cells. J Exp Med. 2007, 204: 1849-1861. 10.1084/jem.20070663.PubMedCentralCrossRefPubMed Annunziato F, Cosmi L, Santarlasci V, Maggi L, Liotta F, Mazzinghi B, Parente E, Fili L, Ferri S, Frosali F, Giudici F, Romagnani P, Parronchi P, Tonelli F, Maggi E: Phenotypic and functional features of human Th17 cells. J Exp Med. 2007, 204: 1849-1861. 10.1084/jem.20070663.PubMedCentralCrossRefPubMed
21.
go back to reference Singh SP, Zhang HH, Foley JF, Hedrick MN, Farber JM: Human T cells that are able to produce IL-17 express the chemokine receptor CCR6. J Immunol. 2008, 180: 214-221.CrossRefPubMed Singh SP, Zhang HH, Foley JF, Hedrick MN, Farber JM: Human T cells that are able to produce IL-17 express the chemokine receptor CCR6. J Immunol. 2008, 180: 214-221.CrossRefPubMed
22.
go back to reference Duerr RH, Taylor KD, Brant SR, Rioux JD, Silverberg MS, Daly MJ, Steinhart AH, Abraham C, Regueiro M, Griffiths A, Dassopoulos T, Bitton A, Yang HY, Targan S, Datta LW, Kistner EO, Schumm LP, Lee AT, Gregersen PK, Barmada MM, Rotter JI, Nicolae DL, Cho JH: A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science. 2006, 314: 1461-1463. 10.1126/science.1135245.PubMedCentralCrossRefPubMed Duerr RH, Taylor KD, Brant SR, Rioux JD, Silverberg MS, Daly MJ, Steinhart AH, Abraham C, Regueiro M, Griffiths A, Dassopoulos T, Bitton A, Yang HY, Targan S, Datta LW, Kistner EO, Schumm LP, Lee AT, Gregersen PK, Barmada MM, Rotter JI, Nicolae DL, Cho JH: A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science. 2006, 314: 1461-1463. 10.1126/science.1135245.PubMedCentralCrossRefPubMed
23.
go back to reference Barrett JC, Hansoul S, Nicolae DL, Cho JH, Duerr RH, Rioux JD, Brant SR, Silverberg MS, Taylor KD, Barmada MM, Bitton A, Dassopoulos T, Datta LW, Green T, Griffiths AM, Kistner EO, Murtha MT, Regueiro MD, Rotter JI, Schumm LP, Steinhart AH, Targan SR, Xavier RJ, Libioulle C, Sandor C, Lathrop M, Belaiche J, Dewit O, Gut I, Heath S, Laukens D, Mni M, Rutgeerts P, Van Gossum A, Zelenika D, Franchimont D, Hugot JP, de Vos M, Vermeire S, Louis E, Cardon LR, Anderson CA, Drummond H, Nimmo E, Ahmad T, Prescott NJ, Onnie CM, Fisher SA, Marchini J, Ghori J, Bumpstead S, Gwilliam R, Tremelling M, Deloukas P, Mansfield J, Jewell D, Satsangi J, Mathew CG, Parkes M, Georges M, Daly MJ: Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease. Nature Genetics. 2008, 40: 955-962. 10.1038/ng.175.PubMedCentralCrossRefPubMed Barrett JC, Hansoul S, Nicolae DL, Cho JH, Duerr RH, Rioux JD, Brant SR, Silverberg MS, Taylor KD, Barmada MM, Bitton A, Dassopoulos T, Datta LW, Green T, Griffiths AM, Kistner EO, Murtha MT, Regueiro MD, Rotter JI, Schumm LP, Steinhart AH, Targan SR, Xavier RJ, Libioulle C, Sandor C, Lathrop M, Belaiche J, Dewit O, Gut I, Heath S, Laukens D, Mni M, Rutgeerts P, Van Gossum A, Zelenika D, Franchimont D, Hugot JP, de Vos M, Vermeire S, Louis E, Cardon LR, Anderson CA, Drummond H, Nimmo E, Ahmad T, Prescott NJ, Onnie CM, Fisher SA, Marchini J, Ghori J, Bumpstead S, Gwilliam R, Tremelling M, Deloukas P, Mansfield J, Jewell D, Satsangi J, Mathew CG, Parkes M, Georges M, Daly MJ: Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease. Nature Genetics. 2008, 40: 955-962. 10.1038/ng.175.PubMedCentralCrossRefPubMed
24.
go back to reference Anderson CA, Massey DCO, Barrett JC, Prescott NJ, Tremelling M, Fisher SA, Gwilliam R, Jacob J, Nimmo ER, Drummond H, Lees CW, Onnie CM, Hanson C, Blaszczyk K, Ravindrarajah R, Hunt S, Varma D, Hammond N, Lewis G, Attlesey H, Watkins N, Ouwehand W, Strachan D, McArdle W, Lewis CM, Lobo A, Sanderson J, Jewell DP, Deloukas P, Mansfield JC, Mathew CG, Satsangi J, Parkes M: Investigation of Crohn's disease risk loci in ulcerative colitis further defines their molecular relationship. Gastroenterol. 2009, 136: 523-529. 10.1053/j.gastro.2008.10.032.CrossRef Anderson CA, Massey DCO, Barrett JC, Prescott NJ, Tremelling M, Fisher SA, Gwilliam R, Jacob J, Nimmo ER, Drummond H, Lees CW, Onnie CM, Hanson C, Blaszczyk K, Ravindrarajah R, Hunt S, Varma D, Hammond N, Lewis G, Attlesey H, Watkins N, Ouwehand W, Strachan D, McArdle W, Lewis CM, Lobo A, Sanderson J, Jewell DP, Deloukas P, Mansfield JC, Mathew CG, Satsangi J, Parkes M: Investigation of Crohn's disease risk loci in ulcerative colitis further defines their molecular relationship. Gastroenterol. 2009, 136: 523-529. 10.1053/j.gastro.2008.10.032.CrossRef
25.
go back to reference Franke A, Balschun T, Karlsen TH, Hedderich J, May S, Lu T, Schuldt D, Nikolaus S, Rosenstiel P, Krawczak M, Schreiber S: Replication of signals from recent studies of Crohn's disease identifies previously unknown disease loci for ulcerative colitis. Nature Genetics. 2008, 40: 713-715. 10.1038/ng.148.CrossRefPubMed Franke A, Balschun T, Karlsen TH, Hedderich J, May S, Lu T, Schuldt D, Nikolaus S, Rosenstiel P, Krawczak M, Schreiber S: Replication of signals from recent studies of Crohn's disease identifies previously unknown disease loci for ulcerative colitis. Nature Genetics. 2008, 40: 713-715. 10.1038/ng.148.CrossRefPubMed
26.
go back to reference Silverberg MS, Cho JH, Rioux JD, McGovern DPB, Wu J, Annese V, Achkar JP, Goyette P, Scott R, Xu W, Barmada MM, Klei L, Daly MJ, Abraham C, Bayless TM, Bossa F, Griffiths AM, Ippoliti AF, Lahaie RG, Latiano A, Pare P, Proctor DD, Regueiro MD, Steinhart AH, Targan SR, Schumm LP, Kistner EO, Lee AT, Gregersen PK, Rotter JI, Brant SR, Taylor KD, Roeder K, Duerr RH: Ulcerative colitis-risk loci on chromosomes 1p36 and 12q15 found by genome-wide association study. Nature Genetics. 2009, 41: 216-220. 10.1038/ng.275.PubMedCentralCrossRefPubMed Silverberg MS, Cho JH, Rioux JD, McGovern DPB, Wu J, Annese V, Achkar JP, Goyette P, Scott R, Xu W, Barmada MM, Klei L, Daly MJ, Abraham C, Bayless TM, Bossa F, Griffiths AM, Ippoliti AF, Lahaie RG, Latiano A, Pare P, Proctor DD, Regueiro MD, Steinhart AH, Targan SR, Schumm LP, Kistner EO, Lee AT, Gregersen PK, Rotter JI, Brant SR, Taylor KD, Roeder K, Duerr RH: Ulcerative colitis-risk loci on chromosomes 1p36 and 12q15 found by genome-wide association study. Nature Genetics. 2009, 41: 216-220. 10.1038/ng.275.PubMedCentralCrossRefPubMed
27.
go back to reference Glas JN, Stallhofer J, Ripke S, Wetzke M, Pfennig S, Klein W, Epplen JT, Griga T, Schiemann U, Lacher M, Koletzko S, Folwaczny M, Lohse P, Goke B, Ochsenkuhn T, Muller-Myhsok B, Brand S: Novel genetic risk markers for ulcerative colitis in the IL2/IL21 region are in epistasis with IL23R and suggest a common genetic background for ulcerative colitis and celiac disease. Am J Gastroenterol. 2009, 104: 1737-1744. 10.1038/ajg.2009.163.CrossRefPubMed Glas JN, Stallhofer J, Ripke S, Wetzke M, Pfennig S, Klein W, Epplen JT, Griga T, Schiemann U, Lacher M, Koletzko S, Folwaczny M, Lohse P, Goke B, Ochsenkuhn T, Muller-Myhsok B, Brand S: Novel genetic risk markers for ulcerative colitis in the IL2/IL21 region are in epistasis with IL23R and suggest a common genetic background for ulcerative colitis and celiac disease. Am J Gastroenterol. 2009, 104: 1737-1744. 10.1038/ajg.2009.163.CrossRefPubMed
28.
go back to reference Schmechel S, Konrad A, Diegelmann J, Glas J, Wetzke M, Paschos E, Lohse P, Goke B, Brand S: Linking genetic susceptibility to Crohn's disease with Th17 cell function: IL-22 serum levels are increased in Crohn's disease and correlate with disease activity and IL23R genotype status. Inflamm Bowel Dis. 2008, 14: 204-212. 10.1002/ibd.20315.CrossRefPubMed Schmechel S, Konrad A, Diegelmann J, Glas J, Wetzke M, Paschos E, Lohse P, Goke B, Brand S: Linking genetic susceptibility to Crohn's disease with Th17 cell function: IL-22 serum levels are increased in Crohn's disease and correlate with disease activity and IL23R genotype status. Inflamm Bowel Dis. 2008, 14: 204-212. 10.1002/ibd.20315.CrossRefPubMed
29.
go back to reference Fujino S, Andoh A, Bamba S, Ogawa A, Hata K, Araki Y, Bamba T, Fujiyama Y: Increased expression of interleukin-17 in inflammatory bowel disease. Gut. 2003, 52: 65-70. 10.1136/gut.52.1.65.PubMedCentralCrossRefPubMed Fujino S, Andoh A, Bamba S, Ogawa A, Hata K, Araki Y, Bamba T, Fujiyama Y: Increased expression of interleukin-17 in inflammatory bowel disease. Gut. 2003, 52: 65-70. 10.1136/gut.52.1.65.PubMedCentralCrossRefPubMed
30.
go back to reference Dambacher J, Beigel F, Golluscio R, Olszak T, Zitzmann K, Eichhorst ST, Otte JM, Seiderer J, Diepolder H, Auemhammer CJ, Ochsenkuehn T, Goeke B, Brand S: The novel IL-10 related cytokine IL-26 is increased in active inflammatory bowel disease and intestinal epithelial cells express the functional IL-26 receptor complex. Gastroenterol. 2006, 130: A696- Dambacher J, Beigel F, Golluscio R, Olszak T, Zitzmann K, Eichhorst ST, Otte JM, Seiderer J, Diepolder H, Auemhammer CJ, Ochsenkuehn T, Goeke B, Brand S: The novel IL-10 related cytokine IL-26 is increased in active inflammatory bowel disease and intestinal epithelial cells express the functional IL-26 receptor complex. Gastroenterol. 2006, 130: A696-
31.
go back to reference Andoh A, Zhang ZB, Inatomi O, Fujino S, Deguchi Y, Araki Y, Tsujikawa T, Kitoh K, Kim-Mitsuyama S, Takayanagi A, Shimizu N, Fujiyama Y: Interleukin-22, a member of the IL-10 subfamily, induces inflammatory responses in colonic subepithelial myofibroblasts. Gastroenterol. 2005, 129: 969-984. 10.1053/j.gastro.2005.06.071.CrossRef Andoh A, Zhang ZB, Inatomi O, Fujino S, Deguchi Y, Araki Y, Tsujikawa T, Kitoh K, Kim-Mitsuyama S, Takayanagi A, Shimizu N, Fujiyama Y: Interleukin-22, a member of the IL-10 subfamily, induces inflammatory responses in colonic subepithelial myofibroblasts. Gastroenterol. 2005, 129: 969-984. 10.1053/j.gastro.2005.06.071.CrossRef
32.
go back to reference Seiderer J, Elben I, Diegelmann J, Glas J, Stallhofer J, Tillack C, Pfennig S, Jurgens M, Schmechel S, Konrad A, Goke B, Ochsenkuhn T, Muller-Myhsok B, Lohse P, Brand S: Role of the novel th17 cytokine IL-17F in inflammatory bowel disease (IBD): Upregulated colonic IL-17F expression in active Crohn's disease and analysis of the IL17F p. Hisl6lArg polymorphism in IBD. Inflamm Bowel Dis. 2008, 14: 437-445. 10.1002/ibd.20339.CrossRefPubMed Seiderer J, Elben I, Diegelmann J, Glas J, Stallhofer J, Tillack C, Pfennig S, Jurgens M, Schmechel S, Konrad A, Goke B, Ochsenkuhn T, Muller-Myhsok B, Lohse P, Brand S: Role of the novel th17 cytokine IL-17F in inflammatory bowel disease (IBD): Upregulated colonic IL-17F expression in active Crohn's disease and analysis of the IL17F p. Hisl6lArg polymorphism in IBD. Inflamm Bowel Dis. 2008, 14: 437-445. 10.1002/ibd.20339.CrossRefPubMed
33.
go back to reference Brand S, Olszak T, Beigel F, Diebold J, Otte JM, Eichhorst ST, Goke B, Dambacher J: Cell differentiation dependent expressed CCR6 mediates ERK-1/2, SAPK/JNK, and Akt signaling resulting in proliferation and migration of colorectal cancer cells. J Cell Biochem. 2006, 97: 709-723. 10.1002/jcb.20672.CrossRefPubMed Brand S, Olszak T, Beigel F, Diebold J, Otte JM, Eichhorst ST, Goke B, Dambacher J: Cell differentiation dependent expressed CCR6 mediates ERK-1/2, SAPK/JNK, and Akt signaling resulting in proliferation and migration of colorectal cancer cells. J Cell Biochem. 2006, 97: 709-723. 10.1002/jcb.20672.CrossRefPubMed
34.
go back to reference Holtta V, Klemetti P, Sipponen T, Kociubinski G, Westerholm-Ormio M, Solo H, Rasanen L, Kolho KL, Farkkila M, Savilahti E, Vaarala O: IL-23/IL-17 immunity as a hallmark of Crohn's disease. Inflamm Bowel Dis. 2008, 14: 1175-1184. 10.1002/ibd.20475.CrossRefPubMed Holtta V, Klemetti P, Sipponen T, Kociubinski G, Westerholm-Ormio M, Solo H, Rasanen L, Kolho KL, Farkkila M, Savilahti E, Vaarala O: IL-23/IL-17 immunity as a hallmark of Crohn's disease. Inflamm Bowel Dis. 2008, 14: 1175-1184. 10.1002/ibd.20475.CrossRefPubMed
35.
go back to reference Mazzucchelli L, Hauser C, Zgraggen K, Wagner H, Hess M, Laissue JA, Mueller C: Expression of interleukin-8 gene in inflammatory bowel disease is related to the histological grade of active inflammation. Am J Pathol. 1994, 144: 997-1007.PubMedCentralPubMed Mazzucchelli L, Hauser C, Zgraggen K, Wagner H, Hess M, Laissue JA, Mueller C: Expression of interleukin-8 gene in inflammatory bowel disease is related to the histological grade of active inflammation. Am J Pathol. 1994, 144: 997-1007.PubMedCentralPubMed
36.
go back to reference Ishiguro Y: Mucosal proinflammatory cytokine production correlates with endoscopic activity of ulcerative colitis. J Gastroenterol. 1999, 34: 66-74. 10.1007/s005350050218.CrossRefPubMed Ishiguro Y: Mucosal proinflammatory cytokine production correlates with endoscopic activity of ulcerative colitis. J Gastroenterol. 1999, 34: 66-74. 10.1007/s005350050218.CrossRefPubMed
37.
go back to reference Vogelzang A, McGuire HM, Yu D, Sprent J, Mackay CR, King C: A fundamental role for interleukin-21 in the generation of T follicular helper cells. Immunity. 2008, 29: 127-137. 10.1016/j.immuni.2008.06.001.CrossRefPubMed Vogelzang A, McGuire HM, Yu D, Sprent J, Mackay CR, King C: A fundamental role for interleukin-21 in the generation of T follicular helper cells. Immunity. 2008, 29: 127-137. 10.1016/j.immuni.2008.06.001.CrossRefPubMed
38.
go back to reference Nurieva RI, Chung Y, Hwang D, Yang XO, Kang HS, Ma L, Wang YH, Watowich SS, Jetten AM, Tian Q, Dong C: Generation of T follicular helper cells is mediated by interleukin-21 but independent of T helper 1, 2, or 17 cell lineages. Immunity. 2008, 29: 138-149. 10.1016/j.immuni.2008.05.009.PubMedCentralCrossRefPubMed Nurieva RI, Chung Y, Hwang D, Yang XO, Kang HS, Ma L, Wang YH, Watowich SS, Jetten AM, Tian Q, Dong C: Generation of T follicular helper cells is mediated by interleukin-21 but independent of T helper 1, 2, or 17 cell lineages. Immunity. 2008, 29: 138-149. 10.1016/j.immuni.2008.05.009.PubMedCentralCrossRefPubMed
39.
go back to reference Yamazaki T, Yang XO, Chung Y, Fukunaga A, Nurieva R, Pappu B, Martin-Orozco N, Kang HS, Ma L, Panopoulos AD, Craig S, Watowich SS, Jetten AM, Tian Q, Dong C: CCR6 regulates the migration of inflammatory and regulatory T cells. J Immunol. 2008, 181: 8391-8401.PubMedCentralCrossRefPubMed Yamazaki T, Yang XO, Chung Y, Fukunaga A, Nurieva R, Pappu B, Martin-Orozco N, Kang HS, Ma L, Panopoulos AD, Craig S, Watowich SS, Jetten AM, Tian Q, Dong C: CCR6 regulates the migration of inflammatory and regulatory T cells. J Immunol. 2008, 181: 8391-8401.PubMedCentralCrossRefPubMed
40.
go back to reference Sato K, Kawasaki H, Nagayama H, Enomoto M, Morimoto C, Tadokoro K, Juji T, Takahashi TA: TGF-beta 1 reciprocally controls chemotaxis of human peripheral blood monocyte-derived dendritic cells via chemokine receptors. J Immunol. 2000, 164: 2285-2295.CrossRefPubMed Sato K, Kawasaki H, Nagayama H, Enomoto M, Morimoto C, Tadokoro K, Juji T, Takahashi TA: TGF-beta 1 reciprocally controls chemotaxis of human peripheral blood monocyte-derived dendritic cells via chemokine receptors. J Immunol. 2000, 164: 2285-2295.CrossRefPubMed
41.
go back to reference Stevens C, Walz G, Singaram C, Lipman ML, Zanker B, Muggia A, Antonioli D, Peppercorn MA, Strom TB: Tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 expression in inflammatory bowel disease. Dig Dis Sci. 1992, 37: 818-826. 10.1007/BF01300378.CrossRefPubMed Stevens C, Walz G, Singaram C, Lipman ML, Zanker B, Muggia A, Antonioli D, Peppercorn MA, Strom TB: Tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 expression in inflammatory bowel disease. Dig Dis Sci. 1992, 37: 818-826. 10.1007/BF01300378.CrossRefPubMed
42.
go back to reference Dionne S, Hiscott J, D'Agata I, Duhaime A, Seidman EG: Quantitative PCR analysis of TNF-alpha and IL-1 beta mRNA levels in pediatric IBD mucosal biopsies. Dig Dis Sci. 1997, 42: 1557-1566. 10.1023/A:1018895500721.CrossRefPubMed Dionne S, Hiscott J, D'Agata I, Duhaime A, Seidman EG: Quantitative PCR analysis of TNF-alpha and IL-1 beta mRNA levels in pediatric IBD mucosal biopsies. Dig Dis Sci. 1997, 42: 1557-1566. 10.1023/A:1018895500721.CrossRefPubMed
43.
go back to reference Cui G, Olsen T, Christiansen I, Vonen B, Florholmen J, Goll R: Improvement of real-time polymerase chain reaction for quantifying TNF-alpha mRNA expression in inflamed colorectal mucosa: an approach to optimize procedures for clinical use. Scand J Clin Lab Invest. 2006, 66: 249-259. 10.1080/00365510600590472.CrossRefPubMed Cui G, Olsen T, Christiansen I, Vonen B, Florholmen J, Goll R: Improvement of real-time polymerase chain reaction for quantifying TNF-alpha mRNA expression in inflamed colorectal mucosa: an approach to optimize procedures for clinical use. Scand J Clin Lab Invest. 2006, 66: 249-259. 10.1080/00365510600590472.CrossRefPubMed
44.
go back to reference Takatori H, Kanno Y, Watford WT, Tato CM, Weiss G, Ivanov II, Littman DR, O'Shea JJ: Lymphoid tissue inducer-like cells are an innate source of IL-17 and IL-22. J Exp Med. 2009, 206: 35-41. 10.1084/jem.20072713.PubMedCentralCrossRefPubMed Takatori H, Kanno Y, Watford WT, Tato CM, Weiss G, Ivanov II, Littman DR, O'Shea JJ: Lymphoid tissue inducer-like cells are an innate source of IL-17 and IL-22. J Exp Med. 2009, 206: 35-41. 10.1084/jem.20072713.PubMedCentralCrossRefPubMed
45.
go back to reference Takahashi N, Vanlaere I, de Rycke R, Cauwels A, Joosten LAB, Lubberts E, van den Berg WB, Libert C: IL-17 produced by Paneth cells drives TNF-induced shock. J Exp Med. 2008, 205: 1755-1761. 10.1084/jem.20080588.PubMedCentralCrossRefPubMed Takahashi N, Vanlaere I, de Rycke R, Cauwels A, Joosten LAB, Lubberts E, van den Berg WB, Libert C: IL-17 produced by Paneth cells drives TNF-induced shock. J Exp Med. 2008, 205: 1755-1761. 10.1084/jem.20080588.PubMedCentralCrossRefPubMed
46.
go back to reference Eyerich K, Foerster S, Pennino D, Carbone T, Cianferani F, Odorisio T, Traidl-Hoffmann C, Durham S, Schmidt-Weber C, Cavani A: Th22 cells represent a distinct human T lymphocyte subset of tissue-signaling leukocytes. J Invest Dermatol. 2009, 129: S2- Eyerich K, Foerster S, Pennino D, Carbone T, Cianferani F, Odorisio T, Traidl-Hoffmann C, Durham S, Schmidt-Weber C, Cavani A: Th22 cells represent a distinct human T lymphocyte subset of tissue-signaling leukocytes. J Invest Dermatol. 2009, 129: S2-
47.
go back to reference Jurgens M, Laubender RP, Hartl F, Weidinger M, Seiderer J, Wagner J, Wetzke M, Beigel F, Pfennig S, Stallhofer J, Schnitzler F, Tillack C, Lohse P, Goke B, Glas J, Ochsenkuhn T, Brand S: Disease activity, ANCA, and IL23R genotype status determine early response to infliximab in patients with ulcerative colitis. Am J Gastroenterol. 2010, 105: 1811-1819. 10.1038/ajg.2010.95.CrossRefPubMed Jurgens M, Laubender RP, Hartl F, Weidinger M, Seiderer J, Wagner J, Wetzke M, Beigel F, Pfennig S, Stallhofer J, Schnitzler F, Tillack C, Lohse P, Goke B, Glas J, Ochsenkuhn T, Brand S: Disease activity, ANCA, and IL23R genotype status determine early response to infliximab in patients with ulcerative colitis. Am J Gastroenterol. 2010, 105: 1811-1819. 10.1038/ajg.2010.95.CrossRefPubMed
48.
go back to reference Satsangi J, Silverberg MS, Vermeire S, Colombel JF: The Montreal classification of inflammatory bowel disease: controversies, consensus, and implications. Gut. 2006, 55: 749-753. 10.1136/gut.2005.082909.PubMedCentralCrossRefPubMed Satsangi J, Silverberg MS, Vermeire S, Colombel JF: The Montreal classification of inflammatory bowel disease: controversies, consensus, and implications. Gut. 2006, 55: 749-753. 10.1136/gut.2005.082909.PubMedCentralCrossRefPubMed
49.
go back to reference Vermeulen J, Derveaux S, Lefever S, De SE, De PK, Yigit N, De Paepe A, Pattyn F, Speleman F, Vandesompele J: RNA pre-amplification enables large-scale RT-qPCR gene-expression studies on limiting sample amounts. BMC Res Notes. 2009, 2: 235-10.1186/1756-0500-2-235.PubMedCentralCrossRefPubMed Vermeulen J, Derveaux S, Lefever S, De SE, De PK, Yigit N, De Paepe A, Pattyn F, Speleman F, Vandesompele J: RNA pre-amplification enables large-scale RT-qPCR gene-expression studies on limiting sample amounts. BMC Res Notes. 2009, 2: 235-10.1186/1756-0500-2-235.PubMedCentralCrossRefPubMed
50.
go back to reference Vandesompele J, De PK, Pattyn F, Poppe B, Van Roy N, De Paepe A, Speleman F: Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol. 2002, 3: RESEARCH0034-10.1186/gb-2002-3-7-research0034.PubMedCentralCrossRefPubMed Vandesompele J, De PK, Pattyn F, Poppe B, Van Roy N, De Paepe A, Speleman F: Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol. 2002, 3: RESEARCH0034-10.1186/gb-2002-3-7-research0034.PubMedCentralCrossRefPubMed
51.
go back to reference Bustin SA, Benes V, Garson JA, Hellemans J, Huggett J, Kubista M, Mueller R, Nolan T, Pfaffl MW, Shipley GL, Vandesompele J, Wittwer CT: The MIQE guidelines: Minimum Information for publication of Quantitative real-time PCR Experiments. Clin Chem. 2009, 55: 611-622. 10.1373/clinchem.2008.112797.CrossRefPubMed Bustin SA, Benes V, Garson JA, Hellemans J, Huggett J, Kubista M, Mueller R, Nolan T, Pfaffl MW, Shipley GL, Vandesompele J, Wittwer CT: The MIQE guidelines: Minimum Information for publication of Quantitative real-time PCR Experiments. Clin Chem. 2009, 55: 611-622. 10.1373/clinchem.2008.112797.CrossRefPubMed
Metadata
Title
Differential mucosal expression of Th17-related genes between the inflamed colon and ileum of patients with inflammatory bowel disease
Authors
Sara Bogaert
Debby Laukens
Harald Peeters
Lode Melis
Kim Olievier
Nico Boon
Gust Verbruggen
Jo Vandesompele
Dirk Elewaut
Martine De Vos
Publication date
01-12-2010
Publisher
BioMed Central
Published in
BMC Immunology / Issue 1/2010
Electronic ISSN: 1471-2172
DOI
https://doi.org/10.1186/1471-2172-11-61

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