The Immunological Basis of Inflammatory Bowel Disease

Francesca A R Silva, Bruno L Rodrigues, Maria de Lourdes S Ayrizono, Raquel F Leal, Francesca A R Silva, Bruno L Rodrigues, Maria de Lourdes S Ayrizono, Raquel F Leal

Abstract

Inflammatory bowel diseases (IBDs) are chronic ailments, Crohn's disease and ulcerative colitis being the most important. These diseases present an inflammatory profile and they differ according to pathophysiology, the affected area in the gastrointestinal tract, and the depth of the inflammation in the intestinal wall. The immune characteristics of IBD arise from abnormal responses of the innate and adaptive immune system. The number of Th17 cells increases in the peripheral blood of IBD patients, while Treg cells decrease, suggesting that the Th17/Treg proportion plays an important role in the development and maintenance of inflammation. The purpose of this review was to determine the current state of knowledge on the immunological basis of IBD. Many studies have shown the need for further explanation of the development and maintenance of the inflammatory process.

Conflict of interest statement

The authors declare that there is no conflict of interests regarding the publication of this paper.

Figures

Figure 1
Figure 1
Intestinal epithelial barrier and the immune system in inflammatory bowel disease. Ag: antigen; APC: antigen presenting cells; IL: interleukin; IFN-γ: interferon gamma; IgA: immunoglobulin A; M cell: microfold cell; TGF-β: transforming growth factor beta; TGF-α: transforming growth factor-alpha; Th: T helper cell; Treg: regulatory T cells; TNF: tumor necrosis factor.
Figure 2
Figure 2
Toll-like receptor signaling pathways. LPS: lipopolysaccharide; CD14: cluster of differentiation 14; MD-2: lymphocyte antigen 96; TLR: toll-like receptor; TRIF: TIR domain-containing adaptor-inducing IFN-β; TRAM: TRIF-related adaptor molecule; TRAP: tartrate-resistant acid phosphatase; MyD88: myeloid differentiation primary response 88; IRAK4: interleukin-1 receptor-associated kinase 4; IRAKM: interleukin-1 receptor-associated kinase M; IRAK1: interleukin-1 receptor-associated kinase 1; IRAK2: interleukin-1 receptor-associated kinase 2; TOLLIP: toll interacting protein; FADD: Fas-associated protein with death domain; Caspase-8: cysteine-aspartic protease 8; TIRAP: toll-interleukin-1 receptor domain-containing adaptor protein; UBC13: ubiquitin-conjugating enzyme; TRAF6: TNF receptor-associated factor 6; UEV1A: ubiquitin-conjugating enzyme E2 variant 1A; ECSIT: evolutionarily conserved signaling intermediate In toll pathway; IKKγ: nuclear factor kappa-B kinase subunit gamma; IKKβ: nuclear factor kappa-B kinase subunit beta; NEMO: NF-kappa-B essential modulator; IKKα: nuclear factor kappa-B kinase subunit alpha; TK1: thymidine kinase 1; TAB1: TGF-beta activated kinase 1; MKK4/7: mitogen-activated protein kinase kinases 4; JNK: Janus kinase; ub: ubiquinization; ICBα: inhibitor of kappa-B; p65/RELA: nuclear factor NF-kappa-B P65 subunit; NF-kB: nuclear factor kappa-B; IL: interleukin; TNF-α: tumor necrosis factor-alpha.

References

    1. Baumgart D. C., Sandborn W. J. Inflammatory bowel disease: clinical aspects and established and evolving therapies. Lancet. 2007;369(9573):1641–1657. doi: 10.1016/S0140-6736(07)60751-X.
    1. Loftus E. V., Jr. Clinical epidemiology of inflammatory bowel disease: incidence, prevalence, and environmental influences. Gastroenterology. 2004;126(6):1504–1517. doi: 10.1053/j.gastro.2004.01.063.
    1. Schirbel A., Fiocchi C. Inflammatory bowel disease: established and evolving considerations on its etiopathogenesis and therapy. Journal of Digestive Diseases. 2010;11(5):266–276. doi: 10.1111/j.1751-2980.2010.00449.x.
    1. Sands B. E. From symptom to diagnosis: clinical distinctions among various forms of intestinal inflammation. Gastroenterology. 2004;126(6):1518–1532. doi: 10.1053/j.gastro.2004.02.072.
    1. Low D., Nguyen D. D., Mizoguchi E. Animal models of ulcerative colitis and their application in drug research. Drug Design, Development and Therapy. 2013;7:1341–1356. doi: 10.2147/DDDT.S40107.
    1. Danese S., Fiocchi C. Ulcerative colitis. The New England Journal of Medicine. 2011;365(18):1713–1725. doi: 10.1056/nejmra1102942.
    1. Cosnes J., Gower-Rousseau C., Seksik P., Cortot A. Epidemiology and natural history of inflammatory bowel diseases. Gastroenterology. 2011;140(6):1785–1794. doi: 10.1053/j.gastro.2011.01.055.
    1. Hisamatsu T., Kanai T., Mikami Y., Yoneno K., Matsuoka K., Hibi T. Immune aspects of the pathogenesis of inflammatory bowel disease. Pharmacology and Therapeutics. 2013;137(3):283–297. doi: 10.1016/j.pharmthera.2012.10.008.
    1. Geremia A., Biancheri P., Allan P., Corazza G. R., Di Sabatino A. Innate and adaptive immunity in inflammatory bowel disease. Autoimmunity Reviews. 2014;13(1):3–10. doi: 10.1016/j.autrev.2013.06.004.
    1. Rodríguez-Feo J. A., Puerto M., Fernández-Mena C., et al. A new role for reticulon-4B/NOGO-B in the intestinal epithelial barrier function and inflammatory bowel disease. American Journal of Physiology—Gastrointestinal and Liver Physiology. 2015;308(12):G981–G993. doi: 10.1152/ajpgi.00309.2014.
    1. Bamias G., Cominelli F. Immunopathogenesis of inflammatory bowel disease: current concepts. Current Opinion in Gastroenterology. 2007;23(4):365–369. doi: 10.1097/mog.0b013e3281c55eb2.
    1. Salim S. Y., Söderholm J. D. Importance of disrupted intestinal barrier in inflammatory bowel diseases. Inflammatory Bowel Diseases. 2011;17(1):362–381. doi: 10.1002/ibd.21403.
    1. Medzhitov R., Preston-Hurlburt P., Janeway C. A., Jr. A human homologue of the Drosophila toll protein signals activation of adaptive immunity. Nature. 1997;388(6640):394–397. doi: 10.1038/41131.
    1. Poltorak A., Smirnova I., He X., et al. Genetic and physical mapping of the Lps locus: identification of the toll-4 receptor as a candidate gene in the critical region. Blood Cells, Molecules, and Diseases. 1998;24(3):340–355. doi: 10.1006/bcmd.1998.0201.
    1. Cario E. Toll-like receptors in inflammatory bowel diseases: a decade later. Inflammatory Bowel Diseases. 2010;16(9):1583–1597. doi: 10.1002/ibd.21282.
    1. Gribar S. C., Anand R. J., Sodhi C. P., Hackam D. J. The role of epithelial Toll-like receptor signaling in the pathogenesis of intestinal inflammation. Journal of Leukocyte Biology. 2008;83(3):493–498. doi: 10.1189/jlb.0607358.
    1. Head K., Jurenka J. Inflammatory bowel disease part II: Crohn's disease—pathophysiology and conventional and alternative treatment options. Alternative Medicine Review. 2004;9(4):360–401.
    1. Miyoshi J., Chang E. B. The gut microbiota and inflammatory bowel diseases. Translational Research. 2016 doi: 10.1016/j.trsl.2016.06.002.
    1. Sung M.-K., Park M.-Y. Nutritional modulators of ulcerative colitis: clinical efficacies and mechanistic view. World Journal of Gastroenterology. 2013;19(7):994–1004. doi: 10.3748/wjg.v19.i7.994.
    1. Sartor R. B. Mechanisms of disease: pathogenesis of Crohn's disease and ulcerative colitis. Nature Clinical Practice Gastroenterology and Hepatology. 2006;3(7):390–407. doi: 10.1038/ncpgasthep0528.
    1. Cho J. H. The genetics and immunopathogenesis of inflammatory bowel disease. Nature Reviews Immunology. 2008;8(6):458–466. doi: 10.1038/nri2340.
    1. Ward M. A., Pierre J. F., Leal R. F., et al. Insights into the pathogenesis of ulcerative colitis from a murine model of stasis-induced dysbiosis, colonic metaplasia, and genetic susceptibility. American Journal of Physiology—Gastrointestinal and Liver Physiology. 2016;310(11):G973–G988. doi: 10.1152/ajpgi.00017.2016.
    1. Devkota S., Wang Y., Musch M. W., et al. Dietary-fat-induced taurocholic acid promotes pathobiont expansion and colitis in Il10-/- mice. Nature. 2012;486(7405):104–108. doi: 10.1038/nature11225.
    1. von Mutius E. Allergies, infections and the hygiene hypothesis—the epidemiological evidence. Immunobiology. 2007;212(6):433–439. doi: 10.1016/j.imbio.2007.03.002.
    1. Strober W., Fuss I., Mannon P. The fundamental basis of inflammatory bowel disease. Journal of Clinical Investigation. 2007;117(3):514–521. doi: 10.1172/JCI30587.
    1. Weaver C. T., Harrington L. E., Mangan P. R., Gavrieli M., Murphy K. M. Th17: an effector CD4 T cell lineage with regulatory T cell ties. Immunity. 2006;24(6):677–688. doi: 10.1016/j.immuni.2006.06.002.
    1. Stockinger B., Veldhoen M. Differentiation and function of Th17 T cells. Current Opinion in Immunology. 2007;19(3):281–286. doi: 10.1016/j.coi.2007.04.005.
    1. Atarashi K., Tanoue T., Shima T., et al. Induction of colonic regulatory T cells by indigenous Clostridium species. Science. 2011;331(6015):337–341. doi: 10.1126/science.1198469.
    1. Ivanov I. I., Atarashi K., Manel N., et al. Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell. 2009;139(3):485–498. doi: 10.1016/j.cell.2009.09.033.
    1. Machiels K., Joossens M., Sabino J., et al. A decrease of the butyrate-producing species Roseburia hominis and Faecalibacterium prausnitzii defines dysbiosis in patients with ulcerative colitis. Gut. 2014;63(8):1275–1283. doi: 10.1136/gutjnl-2013-304833.
    1. Fagarasan S., Kawamoto S., Kanagawa O., Suzuki K. Adaptive immune regulation in the gut: T cell-dependent and T cell-independent IgA synthesis. Annual Review of Immunology. 2010;28:243–273. doi: 10.1146/annurev-immunol-030409-101314.
    1. Strugnell R. A., Wijburg O. L. C. The role of secretory antibodies in infection immunity. Nature Reviews Microbiology. 2010;8(9):656–667. doi: 10.1038/nrmicro2384.
    1. Peterson D. A., McNulty N. P., Guruge J. L., Gordon J. I. IgA response to symbiotic bacteria as a mediator of gut homeostasis. Cell Host & Microbe. 2007;2(5):328–339. doi: 10.1016/j.chom.2007.09.013.
    1. Satoh-Takayama N., Vosshenrich C. A. J., Lesjean-Pottier S., et al. Microbial flora drives interleukin 22 production in intestinal NKp46+ cells that provide innate mucosal immune defense. Immunity. 2008;29(6):958–970. doi: 10.1016/j.immuni.2008.11.001.
    1. Powrie F., Leach M. W., Mauze S., Caddle L. B., Coffman R. L. Phenotypically distinct subsets of CD4+ T cells induce or protect from chronic intestinal inflammation in C. B-17 scid mice. International Immunology. 1993;5(11):1461–1471. doi: 10.1093/intimm/5.11.1461.
    1. Kiss E. A., Vonarbourg C., Kopfmann S., et al. Natural aryl hydrocarbon receptor ligands control organogenesis of intestinal lymphoid follicles. Science. 2011;334(6062):1561–1565. doi: 10.1126/science.1214914.
    1. Qiu J., Heller J. J., Guo X., et al. The aryl hydrocarbon receptor regulates gut immunity through modulation of innate lymphoid cells. Immunity. 2012;36(1):92–104. doi: 10.1016/j.immuni.2011.11.011.
    1. Medzhitov R., Janeway C., Jr. Innate immunity. The New England Journal of Medicine. 2000;343(5):338–344. doi: 10.1056/nejm200008033430506.
    1. Liu L., Liang L. Inflammatory bowel disease and intestinal mucosal immunity cells. World Chinese Journal of Digestology. 2008;16:3181–3186.
    1. Smith P. D., Ochsenbauer-Jambor C., Smythies L. E. Intestinal macrophages: unique effector cells of the innate immune system. Immunological Reviews. 2005;206:149–159. doi: 10.1111/j.0105-2896.2005.00288.x.
    1. Selby W. S., Poulter L. W., Hobbs S., Jewell D. P., Janossy G. Heterogeneity of HLA-DR-positive histiocytes in human intestinal lamina propria: a combined histochemical and immunohistological analysis. Journal of Clinical Pathology. 1983;36(4):379–384. doi: 10.1136/jcp.36.4.379.
    1. Hart A. L., Al-Hassi H. O., Rigby R. J., et al. Characteristics of intestinal dendritic cells in inflammatory bowel diseases. Gastroenterology. 2005;129(1):50–65. doi: 10.1053/j.gastro.2005.05.013.
    1. Zhang S. Z., Zhao X. H., Zhang D. C. Cellular and molecular immunopathogenesis of ulcerative colitis. Cellular & molecular immunology. 2006;3(1):35–40.
    1. Karin M., Ben-Neriah Y. Phosphorylation meets ubiquitination: the control of NF-κB activity. Annual Review of Immunology. 2000;18:621–663. doi: 10.1146/annurev.immunol.18.1.621.
    1. Ghosh S., May M. J., Kopp E. B. NF-κB and rel proteins: evolutionarily conserved mediators of immune responses. Annual Review of Immunology. 1998;16:225–260. doi: 10.1146/annurev.immunol.16.1.225.
    1. Caamaño J., Hunter C. A. NF-κB family of transcription factors: central regulators of innate and adaptive immune functions. Clinical Microbiology Reviews. 2002;15(3):414–429. doi: 10.1128/cmr.15.3.414-429.2002.
    1. Papadakis K. A., Targan S. R. Tumor necrosis factor: biology and therapeutic inhibitors. Gastroenterology. 2000;119(4):1148–1157. doi: 10.1053/gast.2000.18160.
    1. Blam M. E., Stein R. B. S., Lichtenstein G. R. Integrating anti-tumor necrosis factor therapy in inflammatory bowel disease: current and future perspectives. The American Journal of Gastroenterology. 2001;96(7):1977–1997. doi: 10.1016/s0002-9270(01)02494-7.
    1. Huang Y., Chen Z. Inflammatory bowel disease related innate immunity and adaptive immunity. American Journal of Translational Research. 2016;8(6):2490–2497.
    1. Ivanov I. I., McKenzie B. S., Zhou L., et al. The orphan nuclear receptor RORγt directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell. 2006;126(6):1121–1133. doi: 10.1016/j.cell.2006.07.035.
    1. Strober W., Fuss I. J. Proinflammatory cytokines in the pathogenesis of inflammatory bowel diseases. Gastroenterology. 2011;140(6):1756–1767. doi: 10.1053/j.gastro.2011.02.016.
    1. Mosmann T. R., Sad S. The expanding universe of T-cell subsets: Th1, Th2 and more. Immunology Today. 1996;17(3):138–146. doi: 10.1016/0167-5699(96)80606-2.
    1. Romagnani S. The Th1/Th2 paradigm. Immunology Today. 1997;18:263–266.
    1. Paul W. E., Seder R. A. Lymphocyte responses and cytokines. Cell. 1994;76(2):241–251. doi: 10.1016/0092-8674(94)90332-8.
    1. Breese E., Braegger C. P., Corrigan C. J., Walker-Smith J. A., MacDonald T. T. Interleukin-2- and interferon-gamma-secreting T cells in normal and diseased human intestinal mucosa. Immunology. 1993;78(1):127–131.
    1. Fuss I. J., 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. The Journal of Immunology. 1996;157(3):1261–1270.
    1. Monteleone I., Vavassori P., Biancone L., Monteleone G., Pallone F. Immunoregulation in the gut: success and failures in human disease. Gut. 2002;50(3):60–64.
    1. Di Sabatino A., Biancheri P., Rovedatti L., MacDonald T. T., Corazza G. R. New pathogenic paradigms in inflammatory bowel disease. Inflammatory Bowel Diseases. 2012;18(2):368–371. doi: 10.1002/ibd.21735.
    1. Kanai T., Kawamura T., Dohi T., et al. TH1/TH2‐mediated colitis induced by adoptive transfer of CD4+CD45RBhigh T lymphocytes into nude mice. Inflammatory Bowel Diseases. 2006;12(2):89–99. doi: 10.1097/.
    1. Xie C., Zhuang Y., Luan Y. The research progress of the immune factors in the pathogenesis of ulcerative colitis. Cellular & Molecular Immunology. 2013;29:889–892.
    1. Torres M., Rios A. Current view of the immunopathogenesis in inflammatory bowel disease and its implications for therapy. World Journal of Gastroenterology. 2008;14(13):1972–1980. doi: 10.3748/wjg.14.1972.
    1. Bär F., Sina C., Hundorfean G., et al. Inflammatory bowel diseases influence major histocompatibility complex class I (MHC I) and II compartments in intestinal epithelial cells. Clinical and Experimental Immunology. 2013;172(2):280–289. doi: 10.1111/cei.12047.
    1. Thelemann C., Eren R. O., Coutaz M., et al. Interferon-γ induces expression of MHC class II on intestinal epithelial cells and protects mice from colitis. PLOS ONE. 2014;9(1) doi: 10.1371/journal.pone.0086844.e86844
    1. Maloy K. J., Powrie F. Intestinal homeostasis and its breakdown in inflammatory bowel disease. Nature. 2011;474(7351):298–306. doi: 10.1038/nature10208.
    1. Büning J., Hundorfean G., Schmitz M., et al. Antigen targeting to MHC class II-enriched late endosomes in colonic epithelial cells: trafficking of luminal antigens studied in vivo in Crohn's colitis patients. FASEB Journal. 2006;20(2):359–361. doi: 10.1096/fj.05-4807fje.
    1. Goto Y., Panea C., Nakato G., et al. Segmented filamentous bacteria antigens presented by intestinal dendritic cells drive mucosal Th17 cell differentiation. Immunity. 2014;40(4):594–607. doi: 10.1016/j.immuni.2014.03.005.
    1. Peloquin J. M., Goel G., Villablanca E. J., Xavier R. J. Mechanisms of pediatric inflammatory bowel disease. Annual Review of Immunology. 2016;34(1):31–64. doi: 10.1146/annurev-immunol-032414-112151.
    1. Kolls J. K., Lindén A. Interleukin-17 family members and inflammation. Immunity. 2004;21(4):467–476. doi: 10.1016/j.immuni.2004.08.018.
    1. Shih D. Q., Targan S. R. Immunopathogenesis of inflammatory bowel disease. World Journal of Gastroenterology. 2008;14(3):390–400. doi: 10.3748/wjg.14.390.
    1. MacDermott R. P., Nash G. S., Bertovich M. J., Seiden M. V., Bragdon M. J., Beale M. G. Alterations of IgM, IgG, and IgA synthesis and secretion by peripheral blood and intestinal mononuclear cells from patients with ulcerative colitis and Crohn's disease. Gastroenterology. 1981;81(5):844–852.
    1. Scott M. G., Nahm M. H., Macke K., Nash G. S., Bertovich M. J., MacDermott R. P. Spontaneous secretion of IgG subclasses by intestinal mononuclear cells: differences between ulcerative colitis, Crohn's disease, and controls. Clinical and Experimental Immunology. 1986;66(1):209–215.
    1. Tsianos E. V., Katsanos K. Do we really understand what the immunological disturbances in inflammatory bowel disease mean? World Journal of Gastroenterology. 2009;15(5):521–525. doi: 10.3748/wjg.15.521.
    1. Papp M., Altorjay I., Norman G. L., Lakatos P. L. Utility of serological markers in inflammatory bowel diseases: gadget or magic? World Journal of Gastroenterology. 2007;13(14):2028–2036. doi: 10.3748/wjg.v13.i14.2028.
    1. Turkay C., Kasapoglu B. Noninvasive methods in evaluation of inflammatory bowel disease: where do we stand now? An update. Clinics. 2010;65(2):221–231. doi: 10.1590/s1807-59322010000200015.
    1. Iskandar H. N., Ciorba M. A. Biomarkers in inflammatory bowel disease: current practices and recent advances. Translational Research. 2012;159(4):313–325. doi: 10.1016/j.trsl.2012.01.001.
    1. Coukos J. A., Howard L. A., Weinberg J. M., Becker J. M., Stucchi A. F., Farraye F. A. ASCA IgG and CBir antibodies are associated with the development of crohn's disease and fistulae following ileal pouch-anal anastomosis. Digestive Diseases and Sciences. 2012;57(6):1544–1553. doi: 10.1007/s10620-012-2050-6.
    1. Dotan I. New serologic markers for inflammatory bowel disease diagnosis. Digestive Diseases. 2010;28(3):418–423. doi: 10.1159/000320396.
    1. Li Y.-Z., Sun K.-X., Zhao C. Expression of Foxp3 mRNA in peripheral blood monocytes of patients with ulcerative colitis. World Chinese Journal of Digestology. 2006;14(8):810–813.
    1. Boden E. K., Snapper S. B. Regulatory T cells in inflammatory bowel disease. Current Opinion in Gastroenterology. 2008;24(6):733–741. doi: 10.1097/MOG.0b013e328311f26e.
    1. Valencia X., Stephens G., Goldbach-Mansky R., Wilson M., Shevach E. M., Lipsky P. E. TNF downmodulates the function of human CD4+CD25hi T-regulatory cells. Blood. 2006;108(1):253–261. doi: 10.1182/blood-2005-11-4567.
    1. O'Garra A., Vieira P. Regulatory T cells and mechanisms of immune system control. Nature Medicine. 2004;10(8):801–805. doi: 10.1038/nm0804-801.
    1. Izcue A., Coombes J. L., Powrie F. Regulatory T cells suppress systemic and mucosal immune activation to control intestinal inflammation. Immunological Reviews. 2006;212:256–271. doi: 10.1111/j.0105-2896.2006.00423.x.
    1. Fantini M. C., Becker C., Tubbe I., et al. Transforming growth factor β induced FoxP3+ regulatory T cells suppress Th1 mediated experimental colitis. Gut. 2006;55(5):671–680. doi: 10.1136/gut.2005.072801.
    1. Singh B., Read S., Asseman C., et al. Control of intestinal inflammation by regulatory T cells. Immunological Reviews. 2001;182:190–200. doi: 10.1034/j.1600-065X.2001.1820115.x.
    1. Chamouard P., Monneaux F., Richert Z., et al. Diminution of circulating CD4+ CD25high T cells in naïve Crohn's disease. Digestive Diseases and Sciences. 2009;54(10):2084–2093. doi: 10.1007/s10620-008-0590-6.
    1. Fantini M. C., Rizzo A., Fina D., et al. Smad7 controls resistance of colitogenic T cells to regulatory T cell-mediated suppression. Gastroenterology. 2009;136(4):1308–1316.e3. doi: 10.1053/j.gastro.2008.12.053.
    1. Fujino S., Andoh A., Bamba S., et al. Increased expression of interleukin 17 in inflammatory bowel disease. Gut. 2003;52(1):65–70. doi: 10.1136/gut.52.1.65.
    1. 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(12):1682–1689. doi: 10.1136/gut.2007.135053.
    1. Korn T., Bettelli E., Oukka M., Kuchroo V. K. IL-17 and Th17 cells. Annual Review of Immunology. 2009;27:485–517. doi: 10.1146/annurev.immunol.021908.132710.
    1. Rieder F., Fiocchi C. Intestinal fibrosis in inflammatory bowel disease—current knowledge and future perspectives. Journal of Crohn's and Colitis. 2008;2(4):279–290. doi: 10.1016/j.crohns.2008.05.009.
    1. Rieder F., Brenmoehl J., Leeb S., Schölmerich J., Rogler G. Wound healing and fibrosis in intestinal disease. Gut. 2007;56(1):130–139. doi: 10.1136/gut.2006.090456.
    1. Lawrance I. C., Maxwell L., Doe W. Altered response of intestinal mucosal fibroblasts to profibrogenic cytokines in inflammatory bowel disease. Inflammatory Bowel Diseases. 2001;7(3):226–236. doi: 10.1097/00054725-200108000-00008.
    1. McKaig B. C., Hughes K., Tighe P. J., Mahida A. Y. R. Differential expression of TGF-β isoforms by normal and inflammatory bowel disease intestinal myofibroblasts. American Journal of Physiology—Cell Physiology. 2002;282(1):C172–C182. doi: 10.1152/ajpcell.00048.2001.
    1. Simmons J. G., Pucilowska J. B., Keku T. O., Kay Lund P. IGF-I and TGF-β1 have distinct effects on phenotype and proliferation of intestinal fibroblasts. American Journal of Physiology—Gastrointestinal and Liver Physiology. 2002;283(3):G809–G818.
    1. Theiss A. L., Simmons J. G., Jobin C., Lund P. K. Tumor necrosis factor (TNF) α increases collagen accumulation and proliferation in intestinal myofibroblasts via TNF receptor 2. Journal of Biological Chemistry. 2005;280(43):36099–36109. doi: 10.1074/jbc.M505291200.
    1. Leeb S. N., Vogl D., Gunckel M., et al. Reduced migration of fibroblasts in inflammatory bowel disease: role of inflammatory mediators and focal adhesion kinase. Gastroenterology. 2003;125(5):1341–1354. doi: 10.1016/j.gastro.2003.07.004.

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