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01-07-2008 | Original Paper

Dendritic Cells and Toll-Like Receptors 2 and 4 in the Ileum of Crohn's Disease Patients

Authors: Manuel A. Silva, Rodrigo Quera, Jorge Valenzuela, Sa’ad Y. Salim, Johan D. Söderholm, Mary H. Perdue

Published in: Digestive Diseases and Sciences | Issue 7/2008

Abstract

We investigated myeloid-dendritic cell (DC) marker and Toll-like receptor (TLR)-2 and 4 distributions in ileal samples from Crohn's disease (CD) patients (n = 14) and controls (n = 13). In controls, no TLR-2⁺ cells were observed, and higher numbers of TLR-4⁺ and DC-SIGN⁺ cells (P < 0.01) were detected in ileal samples when compared versus colonic tissues. In non-inflamed CD ileum, TLR-4⁺ and DC-SGN⁺ cells were depleted from superficial areas of the villus, and a significant CD1a⁺ cell infiltration (P < 0.01) was observed when compared to ileal controls and non-inflamed colonic CD samples. In inflamed CD ileum, DC-SIGN⁺, CD1a⁺, TLR-4⁺and few TLR-4⁺DC-SIGN⁺ cells were detected as well as CD83 depletion. No correlation between TLR-2 and DC markers was detected in CD samples. A unique distribution of myeloid-DC markers characterized the CD ileum. Also, the presence of significant amounts of ileal CD1a⁺ cells may provide a relevant DC-mediated mechanism for antigen recognition in the pathogenesis of CD.

Bouma G, Strober W (2003) The immunological and genetic basis of inflammatory bowel disease. Nat Rev Immunol 3:521–533PubMedCrossRef

de Baey A, Mende I, Baretton G, Greiner A, Hartl WH, Baeuerle PA, Diepolder HM (2003) A subset of human dendritic cell in the T cell area of mucosa-associated lymphoid tissue with a high potential to produce TNF-α. J Immunol 170:5089–5094PubMed

te Velde AA, van Kooyk Y, Braat H, Hommes DW, Dellemijn TA, Slors JF, van Deventer SJ, Vyth-Dreese FA (2003) Increased expression of DC-SIGN+IL-12+IL-18+ and CD83+IL-12-IL-18- dendritic cell populations in the colonic mucosa of patients with Crohn’s disease. Eur J Immunol 33:143–151CrossRef

Silva MA, López CB, Riverin F, Oligny L, Menezes J, Seidman EG (2004) Characterization and distribution of colonic dendritic cells in Crohn's disease. Inflamm Bowel Dis 10:504–512PubMedCrossRef

Baumgart DC, Metzke D, Schmitz J, Scheffold A, Sturm A, Wiedenmann B, Dignass AU (2005) Patients with active inflammatory bowel disease lack immature peripheral blood plasmacytoid and myeloid dendritic cells. Gut 54:228–236PubMedCrossRef

Hart AL, Al-Hassi HO, Rigby RJ, Bell SJ, Emmanuel AV, Knight SC, Kamm MA, Stagg AJ (2005) Characteristics of intestinal dendritic cells in inflammatory bowel disease. Gastroenterology 129:50–65PubMedCrossRef

Middel P, Raddatz D, Gunawan B, Haller F, Radzun HJ (2006) Increased number of mature dendritic cells in Crohn´s disease: evidence for a chemokine mediated retention mechanism. Gut 55:220–227PubMedCrossRef

Guermonprez P, Valladeau J, Zitvogel L (2002) Antigen presentation and T cell stimulation by dendritic cells. Annu Rev Immunol 20:621–667PubMedCrossRef

Liu L, MacPherson G (1995) Rat intestinal dendritic cells: immunostimulatory potency and phenotypic characterization. Immunology 85:88–93PubMed

10.

Takeda K, Kaisho T, Akira S (2003) Toll-like receptors. Ann Rev Immunol 21:335–376CrossRef

11.

Parker L, Prince L, Sabroe I (2007) Translational mini-review series on Toll-Like receptors: Networks regulated by Toll-like receptors mediate innate and adaptive immunity. Clin Exp Immunol 147:199–207PubMedCrossRef

12.

Franchimont D, Vermeire S, El Housni H, Pierik M, Van Steen K, Gustot T, Quertinmont E, Abramowicz M, Van Gossum A, Devière J, Rutgeerts P (2004) Deficient host-bacteria interactions in inflammatory bowel disease? The toll-like receptor (TLR)-4 Asp299gly polymorphism is associated with Crohn´s disease and ulcerative colitis. Gut 53:987–992PubMedCrossRef

13.

Vermeire S, Rutgeerts P (2005) Current status of genetic research in inflammatory bowel disease. Genes Immun 6:637–645PubMed

14.

Netea MG, Kullberg BJ, de Jong DJ, Franke B, Sprong T, Naber TH, Drenth JP, Van der Meer JW (2004) NOD2 mediates anti-inflammatory signals induced by TLR-2 ligands: implicatons for Crohn´s disease. Eur J Immunol 34:2052–2059PubMedCrossRef

15.

Cario E, Podolsky D (2006) Toll-like receptor signaling and its relevance to intestinal inflammation. Ann NY Acad Sci 1072:332–338PubMedCrossRef

16.

Figueroa C, Peralta A, Herrera L, Castro P, Gutiérrez A, Valenzuela J, Aguillón JC, Quera R, Hermoso MA (2006) NOD2/CARD15 and Toll-like 4 receptor gene polymorphism in chilean patients with inflammatory bowel disease. Eur Cytokine Netw 17:125–130PubMed

17.

Török HP, Glas J, Tonenchi L, Mussack T, Folwaczny C (2004) Polymorphisms of the lipopolysaccharide-signaling complex in inflammatory bowel disease: association of a mutation in the Toll-like receptor 4 gene with ulcerative colitis. Clin Immunol 112:85–91PubMedCrossRef

18.

Hollander D, Vadheim CM, Brettholz E, Petersen GM, Delahunty T, Rotter JI (1986) Increased intestinal permeability in patients with Crohn´s disease and their relatives. A possible etiological factor. Ann Intern Med 105:883–885PubMed

19.

Meddings J (1997) Review articule: intestinal permeability in Crohn´s disease. Aliment Pharmacol Ther 11(suppl3):47–53PubMed

20.

Söderholm JD, Streutker C, Yang PC, Paterson C, Singh PK, McKay DM, Sherman PM, Croitoru K, Perdue MH (2004) Increased epithelial uptake of protein antigens in the ileum of Crohn´s disease mediated by tumor necrosis factor α. Gut 53:1817–1824PubMedCrossRef

21.

Hausmann M, Kiessling S, Mestermann S, Webb G, Spöttl T, Andus T, Schölmerich J, Herfarth H, Ray K, Falk W, Rogler G (2002) Toll-like receptors 2 and 4 are up-regulated during intestinal inflammation. Gastroenterology 122:1987–2000PubMedCrossRef

22.

Cario E, Podolsky D (2000) Differential alteration in intestinal epithelial cell expression of Toll-like receptor 3 (TLR3) and TLR4 in inflammatory bowel disease. Infect Immun 68:7010–7017PubMedCrossRef

23.

Moody B (2006) TLR gateways to CD1 function. Nat Immunol 7:811–817PubMedCrossRef

24.

Lechmann M, Berchtold S, Hauber J, Steinkasserer A (2002) CD83 on dendritic cells: more than just a marker for maturation. Trends Immunol 23:273–275PubMedCrossRef

25.

Geijtenbeek TB, Torensma R, van Vliet SJ, van Duijnhoven GC, Adema GJ, van Kooyk Y, Figdor CG (2000) Identification of DC-SIGN, a novel dendritic cell-specific ICAM-3 receptor that supports primary immune responses. Cell 100:575–585PubMedCrossRef

26.

Silva MA, Menezes J, Wizman S, Gendron R, Oligny L, Seidman EG (2003) Cytokine tissue levels as markers of disease activity in pediatric Crohn disease. Pediatr Res 54:456–461PubMedCrossRef

27.

Silva MA, Porras M, Jury J, Vergara P, Perdue MH (2006) Characterization of ileal dendritic cell distribution in a rat model of acute and chronic inflammation. Inflamm Bowel Dis 12:457–470PubMedCrossRef

28.

Bell SJ, Rigby R, English N, Mann SD, Knight SC, Kamm MA, Stagg AJ (2001) Migration and maturation of human colonic dendritic cells. J Immunol 166:4958–4967PubMed

29.

Stagg AJ, Hart AL, Knight SC, Kamm MA (2003) The dendritic cell: its role in the intestinal inflammation and relationship with gut bacteria. Gut 52:1522–1529PubMedCrossRef

30.

Steinman R, Hemmi H (2006) Dendritic cells: translating innate to adaptive immunity. Curr Top Microbiol Immunol 311:17–58PubMedCrossRef

31.

Duchmann R, Kaiser I, Hermann E, Mayet W, Ewe K, Meyer zum Büschenfelde KH (1995) Tolerance exists towards resident itestinal flora but is broken in active inflammatory bowel disease (IBD). Clin Exp Immunol 102:448–455PubMedCrossRef

32.

Landers CJ, Cohavy O, Misra R, Yang H, Lin YC, Braun J, Targan SR (2002) Selected loss of tolerance evidenced by Crohn´s disease-associated immune responses to auto- and microbial antigens. Gastroenterology 123:689–699PubMedCrossRef

33.

Ramakrishna B (2007) The normal bacterial flora of the human intestine and its regulation. J Clin Gastroenterol 41(Suppl 1):S2-S6CrossRef

34.

Savage D (1977) Microbial ecology of the gastrointestinal tract. Annu Rev Microbiol 31:107–133PubMedCrossRef

35.

Abreu MT, Vora P, Faure E, Thomas LS, Arnold ET, Arditi M (2001) Decreased expression of Toll-like receptor-4 and MD-2 correlates with intestinal epithelial cell protection against dysregulated proinflammatory gene expression in response to bacterial lipopolysaccharide. J Immunol 167:1609–1616PubMed

36.

Abreu MT, Arnold ET, Thomas LS, Gonsky R, Zhou Y, Hu B, Arditi M (2002) TLR-4 and MD-2 expression is regulated by immune-mediated signals in human epithelial cells. J Biol Chem 277:20431–20437PubMedCrossRef

37.

Rakoff-Nahoum S, Paglino J, Eslami-Varzaneh F, Edberg S, Medzhitov R (2004) Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis. Cell 118:229–241PubMedCrossRef

38.

Bashir ME, Louie S, Shi HN, Nagler-Anderson C (2004) Toll-like receptor 4 signaling by intestinal microbes influences susceptibility to food allergy. J Immunol 172:6978–6987PubMed

39.

Neal MD, Leaphart C, Levy R, Prince J, Billiar TR, Watkins S, Li J, Cetin S, Ford H, Schreiber A, Hackam DJ (2006) Enterocyte TLR-4 mediates phagocytosis and translocation of bacteria across the intestinal barrier. J Immunol 176:3070–3079PubMed

40.

Corthésy B (2007) Roundtrip ticket for secretory IgA: role in mucosal Homeostasis? J Immunol 178:27–32PubMed

41.

Iweala O, Nagler C (2006) Immune privilege of the gut: the establishment and maintenance of non-responsiveness to dietary antigens and commensal flora. Immunol Rev 213:82–100PubMedCrossRef

42.

Rogler G, Hausmann M, Vogl D, Aschenbrenner E, Andus T, Falk W, Andreesen R, Schölmerich J, Gross V (1998) Isolation and phenotypic characterization of colonic macrophages. Clin Exp Immunol 112:205–215PubMedCrossRef

43.

Rogler G, Andus T, Aschenbrenner E, Vogl D, Falk W, Schölmerich J, Gross V (1997) Alterations of the phenotype of colonic macrophages in inflammatory bowel disease. Eur J Gastroenterol Hepathol 9:893–899

44.

Gewirtz AT, Vijay-Kumar M, Brant SR, Duerr RH, Nicolae DL, Cho JH (2006) Dominant-negative TLR-5 polymorphism reduces adaptive immune response to flagellin and negatively associates with Crohn's disease. Am J Physiol Gastrointest Liver Physiol 290:G1157-G1163PubMedCrossRef

45.

Braat H, Stokkers P, Hommes T, Cohn D, Vogels E, Pronk I, Spek A, van Kampen A, van Deventer S, Peppelenbosch M, Hommes D (2005) Consequence of functional Nod2 and Tlr4 mutations on gene transcription in Crohn´s disease patients. J Mol Med 83:601–609PubMedCrossRef

46.

Watanabe S, Yamakawa M, Hiroaki T, Kawata S, Kimura O (2007). Correlation of dendritic cell infiltration with active crypt inflammation in ulcerative colitis. Clin Immunol 122:288–297PubMedCrossRef

47.

Bedford PA, Todorovic V, Westcott ED, Windsor AC, English NR, Al-Hassi HO, Raju KS, Mills S, Knight SC (2006) Adipose tissue of human omemtum is a major source of dendritic cells, which lose MHC clas II and stimulatory function in Crohn´s disease. J Leukoc Biol 80:546–554PubMedCrossRef

48.

Brigl M, Brenner M (2004) CD1: antigen presentation and T cell function. Ann Rev Immunol 22:817–890CrossRef

Title: Dendritic Cells and Toll-Like Receptors 2 and 4 in the Ileum of Crohn's Disease Patients
Authors: Manuel A. Silva
Rodrigo Quera
Jorge Valenzuela
Sa’ad Y. Salim
Johan D. Söderholm
Mary H. Perdue
Publication date: 01-07-2008
Publisher: Springer US
Published in: Digestive Diseases and Sciences / Issue 7/2008
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI: https://doi.org/10.1007/s10620-007-0105-x

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