The role of transforming growth factor (TGF)-β in modulating the immune response and fibrogenesis in the gut

Cytokine and Growth Factor Reviews

Volumn 25, Issue 1, 2014, Pages 45-55

  Biancheri, Paolo ^a,b   Giuffrida, Paolo ^a   Docena, Guillermo H ^c   MacDonald, Thomas T ^b   Corazza, Gino Roberto ^a   Di Sabatino, Antonio ^a  

^a UNIVERSITY OF PAVIA   (Italy)

^b QUEEN MARY UNIVERSITY OF LONDON   (United Kingdom)

^c UNIVERSIDAD NACIONAL DE LA PLATA   (Argentina)

Author keywords

Celiac disease; Crohn's disease; Myofibroblast; Regulatory T cell; Smad

Indexed keywords

ANGIOTENSIN RECEPTOR ANTAGONIST; BOSWELLIA EXTRACT; CAPTOPRIL; DIGESTIVE TRACT AGENT; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; ENALAPRILAT; FIBROBLAST GROWTH FACTOR 2; GAMMA INTERFERON; GED 0301; GED 0507 34 LEVO; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 15; INTERLEUKIN 17; INTERLEUKIN 25; INTERLEUKIN 8; INTERSTITIAL COLLAGENASE; LOSARTAN; MACROPHAGE ELASTASE; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA AGONIST; PROTEIN GLUTAMINE GAMMA GLUTAMYLTRANSFERASE; RETINOIC ACID; SCUTELLARIA EXTRACT; SECRETORY IMMUNOGLOBULIN; SMAD3 PROTEIN; SMAD7 PROTEIN; TISSUE INHIBITOR OF METALLOPROTEINASE 1; TRANSFORMING GROWTH FACTOR BETA; TRANSFORMING GROWTH FACTOR BETA ANTIBODY; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; UNINDEXED DRUG;

CELIAC DISEASE; CELL MIGRATION; CHRONIC DISEASE; COLONIC FIBROSIS; CROHN DISEASE; DIET SUPPLEMENTATION; DISEASE PREDISPOSITION; DOWN REGULATION; DRUG ACTIVITY; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; EXPERIMENTAL COLITIS; EXTRACELLULAR MATRIX; FIBROGENESIS; HUMAN; IMMUNE RESPONSE; IMMUNOLOGICAL TOLERANCE; IMMUNOMODULATION; IMMUNOPATHOLOGY; IMMUNOREGULATION; INFLAMMATORY BOWEL DISEASE; INTESTINAL FIBROSIS; INTESTINE; INTESTINE CELL; INTESTINE FIBROGENESIS; INTESTINE MUCOSA; INTESTINE STENOSIS; LYMPHOCYTE DIFFERENTIATION; LYMPHOCYTE FUNCTION; MACROPHAGE; MYOFIBROBLAST; NEGATIVE FEEDBACK; NONHUMAN; PATHOPHYSIOLOGY; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN METABOLISM; PROTEIN PHOSPHORYLATION; PROTEIN TARGETING; REGULATORY T LYMPHOCYTE; SHORT SURVEY; SIGNAL TRANSDUCTION; T LYMPHOCYTE; TH17 CELL; TISSUE REPAIR; ULCERATIVE COLITIS; UNSPECIFIED SIDE EFFECT;

CELIAC DISEASE; CROHN'S DISEASE; MYOFIBROBLAST; REGULATORY T CELL; SMAD;

ANIMALS; CELL DIFFERENTIATION; HUMANS; IMMUNE TOLERANCE; INFLAMMATORY BOWEL DISEASES; INTESTINAL MUCOSA; INTESTINES; MICE; SIGNAL TRANSDUCTION; T-LYMPHOCYTES, REGULATORY; TRANSFORMING GROWTH FACTOR BETA; WOUND HEALING;

EID: 84895801386     PISSN: 13596101     EISSN: 18790305     Source Type: Journal    
DOI: 10.1016/j.cytogfr.2013.11.001     Document Type: Short Survey

References (149)

1. Derynck R., Miyazono K. TGF-β and the TGF-β Family. The TGF-β Family 2008, 29-44. Cold Spring Harbor Press, New York. R. Derynck, K. Miyazono (Eds.).
2. Govinden R., Bhoola K.D. Genealogy, expression, and cellular function of transforming growth factor-beta. Pharmacol Ther 2003, 98:257-265.
3. Annes J.P., Munger J.S., Rifkin D.B. Making sense of latent TGFbeta activation. J Cell Sci 2003, 116:217-224.
4. Venkatraman L., Chia S.M., Narmada B.C., White J.K., Bhowmick S.S., Forbes Dewey C., et al. Plasmin triggers a switch-like decrease in thrombospondin-dependent activation of TGF-beta1. Biophys J 2012, 103:1060-1068.
5. Yu Q., Stamenkovic I. Cell surface-localized matrix metalloproteinase-9 proteolytically activates TGF-beta and promotes tumor invasion and angiogenesis. Genes Dev 2000, 14:163-176.
6. Worthington J.J., Klementowicz J.E., Travis M.A. TGFβ: a sleeping giant awoken by integrins. Trends Biochem Sci 2011, 36:47-54.
7. Asano Y., Ihn H., Yamane K., Jinnin M., Mimura Y., Tamaki K. Increased expression of integrin alpha(v)beta3 contributes to the establishment of autocrine TGF-beta signaling in scleroderma fibroblasts. J Immunol 2005, 175:7708-7718.
8. Asano Y., Ihn H., Yamane K., Jinnin M., Mimura Y., Tamaki K. Involvement of alphavbeta5 integrin-mediated activation of latent transforming growth factor beta1 in autocrine transforming growth factor beta signaling in systemic sclerosis fibroblasts. Arthritis Rheum 2005, 52:2897-2905.
9. Munger J.S., Huang X., Kawakatsu H., Griffiths M.J., Dalton S.L., Wu J., et al. The integrin alpha v beta 6 binds and activates latent TGF beta 1: a mechanism for regulating pulmonary inflammation and fibrosis. Cell 1999, 96:319-328.
10. Worthington J.J., Czajkowska B.I., Melton A.C., Travis M.A. Intestinal dendritic cells specialize to activate transforming growth factor-beta and induce Foxp3+ regulatory T cells via integrin alphavbeta8. Gastroenterology 2011, 141:1802-1812.
11. Shi Y., Massagué J. Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell 2003, 113:685-700.
12. Heldin C.H., Miyazono K., ten Dijke P. TGF-beta signalling from cell membrane to nucleus through SMAD proteins. Nature 1997, 390:465-471.
13. Massagué J. TGF-beta signal transduction. Annu Rev Biochem 1998, 67:753-791.
14. Massagué J. TGFβ signalling in context. Nat Rev Mol Cell Biol 2012, 13:616-630.
15. Nakao A., Afrakhte M., Moren A., Nakayama T., Christian J.L., Heuchel R., et al. Identification of Smad7, a TGFbeta-inducible antagonist of TGF-beta signalling. Nature 1997, 389:631-635.
16. Kavsak P., Rasmussen R.K., Causing C.G., Bonni S., Zhu H., Thomsen G.H., et al. Smad7 binds to Smurf2 to form an E3 ubiquitin ligase that targets the TGF beta receptor for degradation. Mol Cell 2000, 6:1365-1375.
17. Shi W., Sun C., He B., Xiong W., Shi X., Yao D., et al. GADD34-PP1c recruited by Smad7 dephosphorylates TGFbeta type I receptor. J Cell Biol 2004, 164:291-300.
18. Moustakas A., Heldin C.H. The regulation of TGFbeta signal transduction. Development 2009, 136:3699-3714.
19. Li M.O., Wan Y.Y., Sanjabi S., Robertson A.K., Flavell R.A. Transforming growth factor-beta regulation of immune responses. Annu Rev Immunol 2006, 24:99-146.
20. Derynck R., Zhang Y.E. Smad-dependent and Smad-independent pathways in TGF-beta family signalling. Nature 2003, 425:577-584.
21. Letterio J.J., Roberts A.B. Regulation of immune responses by TGF-beta. Annu Rev Immunol 1998, 16:137-161.
22. Konkel J.E., Chen W. Balancing acts: the role of TGF-beta in the mucosal immune system. Trends Molecular Med 2011, 17:668-676.
23. Iizuka M., Konno S. Wound healing of intestinal epithelial cells. World J Gastroenterol 2011, 17:2161-2171.
24. Monteleone G., Pallone F., MacDonald T.T. Smad7 in TGF-beta-mediated negative regulation of gut inflammation. Trends Immunol 2004, 25:513-517.
25. Feagins L.A. Role of transforming growth factor-β in inflammatory bowel disease and colitis-associated colon cancer. Inflamm Bowel Dis 2010, 16:1963-1968.
26. Benahmed M., Meresse B., Arnulf B., Barbe U., Mention J.J., Verkarre V., et al. Inhibition of TGF-beta signaling by IL-15: a new role for IL-15 in the loss of immune homeostasis in celiac disease. Gastroenterology 2007, 132:994-1008.
27. Shull M.M., Ormsby I., Kier A.B., Pawlowski S., Diebold R.J., Yin M., et al. Targeted disruption of the mouse transforming growth factor-beta 1 gene results in multifocal inflammatory disease. Nature 1992, 359:693-699.
28. Kulkarni A.B., Karlsson S. Transforming growth factor-beta 1 knockout mice. A mutation in one cytokine gene causes a dramatic inflammatory disease. Am J Pathol 1993, 143:3-9.
29. Gorelik L., Flavell R.A. Abrogation of TGFbeta signaling in T cells leads to spontaneous T cell differentiation and autoimmune disease. Immunity 2000, 12:171-181.
30. Chen W., Jin W., Hardegen N., Lei K.J., Li L., Marinos N., et al. Conversion of peripheral CD4+CD25- naive T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3. J Exp Med 2003, 198:1875-1886.
31. Smythies L.E., Maheshwari A., Clements R., Eckhoff D., Novak L., Vu H.L., et al. Mucosal IL-8 and TGF-beta recruit blood monocytes: evidence for cross-talk between the lamina propria stroma and myeloid cells. J Leukoc Biol 2006, 80:492-499.
32. Smith P.D., Smythies L.E., Shen R., Greenwell-Wild T., Gliozzi M., Wahl S.M. Intestinal macrophages and response to microbial encroachment. Mucosal Immunol 2011, 4:31-42.
33. Smythies L.E., Shen R., Bimczok D., Novak L., Clements R.H., Eckhoff D.E., et al. Inflammation anergy in human intestinal macrophages is due to Smad-induced IkappaBalpha expression and NF-kappaB inactivation. J Biol Chem 2010, 285:19593-19604.
34. Monteleone G., Mann J., Monteleone I., Vavassori P., Bremner R., Fantini M., et al. A failure of transforming growth factor-beta1 negative regulation maintains sustained NF-kappaB activation in gut inflammation. J Biol Chem 2004, 279:3925-3932.
35. Naiki Y., Michelsen K.S., Zhang W., Chen S., Doherty T.M., Arditi M. Transforming growth factor-beta differentially inhibits MyD88-dependent, but not TRAM- and TRIF-dependent, lipopolysaccharide-induced TLR4 signaling. J Biol Chem 2005, 280:5491-5495.
36. Maheshwari A., Kelly D.R., Nicola T., Ambalavanan N., Jain S.K., Murphy-Ullrich J., et al. TGF-β2 suppresses macrophage cytokine production and mucosal inflammatory responses in the developing intestine. Gastroenterology 2011, 140:242-253.
37. Smythies L.E., Sellers M., Clements R.H., Mosteller-Barnum M., Meng G., Benjamin W.H., et al. Human intestinal macrophages display profound inflammatory anergy despite avid phagocytic and bacteriocidal activity. J Clin Invest 2005, 115:66-75.
38. Gebhardt T., Lorentz A., Detmer F., Trautwein C., Bektas H., Manns M.P., et al. Growth, phenotype, and function of human intestinal mast cells are tightly regulated by transforming growth factor beta1. Gut 2005, 54:928-934.
39. Fantini M.C., Becker C., Monteleone G., Pallone F., Galle P.R., Neurath M.F. 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.
40. Izcue A., Coombes J.L., Powrie F. Regulatory lymphocytes and intestinal inflammation. Annu Rev Immunol 2009, 27:313-338.
41. Dominitzki S., Fantini M.C., Neufert C., Nikolaev A., Galle P.R., Scheller J., 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.
42. Huber S., Schramm C., Lehr H.A., Mann A., Schmitt S., Becker C., et al. Cutting edge: TGF-beta signaling is required for the in vivo expansion and immunosuppressive capacity of regulatory CD4+CD25+ T cells. J Immunol 2004, 173:6526-6531.
43. Schlenner S.M., Weigmann B., Ruan Q., Chen Y., von Boehmer H. Smad3 binding to the foxp3 enhancer is dispensable for the development of regulatory T cells with the exception of the gut. J Exp Med 2012, 209:1529-1535.
44. Sun C.M., Hall J.A., Blank R.B., Bouladoux N., Oukka M., Mora J.R., et al. Small intestine lamina propria dendritic cells promote de novo generation of Foxp3 T reg cells via retinoic acid. J Exp Med 2007, 204:1775-1785.
45. Coombes J.L., Siddiqui K.R., Arancibia-Carcamo C.V., Hall J., Sun C.M., Belkaid Y., et al. A functionally specialized population of mucosal CD103+ DCs induces Foxp3+ regulatory T cells via a TGF-beta and retinoic acid-dependent mechanism. J Exp Med 2007, 204:1757-1764.
46. Mucida D., Park Y., Kim G., Turovskaya O., Scott I., Kronenberg M., et al. Reciprocal TH17 and regulatory T cell differentiation mediated by retinoic acid. Science 2007, 317:256-260.
47. Mangan P.R., Harrington L.E., O'Quinn D.B., Helms W.S., Bullard D.C., Elson C.O., et al. Transforming growth factor-beta induces development of the T(H)17 lineage. Nature 2006, 441:231-234.
48. Li M.O., Flavell R.A. Contextual regulation of inflammation: a duet by transforming growth factor-beta and interleukin-10. Immunity 2008, 28:468-476.
49. Rescigno M., Di Sabatino A. Dendritic cells in intestinal homeostasis and disease. J Clin Invest 2009, 119:2441-2450.
50. Bermudez-Brito M., Muñoz-Quezada S., Gomez-Llorente C., Matencio E., Bernal M.J., Romero F., et al. Human intestinal dendritic cells decrease cytokine release against Salmonella infection in the presence of Lactobacillus paracasei upon TLR activation. PLoS ONE 2012, 7:e43197.
51. Bermudez-Brito M., Muñoz-Quezada S., Gomez-Llorente C., Matencio E., Bernal M.J., Romero F., et al. Cell-free culture supernatant of Bifidobacterium breve CNCM I-4035 decreases pro-inflammatory cytokines in human dendritic cells challenged with Salmonella typhi through TLR activation. PLoS ONE 2013, 8:e59370.
52. Travis M.A., Reizis B., Melton A.C., Masteller E., Tang Q., Proctor J.M., et al. Loss of integrin alpha(v)beta8 on dendritic cells causes autoimmunity and colitis in mice. Nature 2007, 449:361-365.
53. Maloy K.J., Salaun L., Cahill R., Dougan G., Saunders N.J., Powrie F. CD4+CD25+ T(R) cells suppress innate immune pathology through cytokine-dependent mechanisms. J Exp Med 2003, 197:111-119.
54. Monteiro M., Almeida C.F., Caridade M., Ribot J.C., Duarte J., Agua-Doce A., et al. Identification of regulatory Foxp3+ invariant NKT cells induced by TGF-beta. J Immunol 2010, 185:2157-2163.
55. Li M.O., Wan Y.Y., Flavell R.A. T cell-produced transforming growth factor-beta1 controls T cell tolerance and regulates Th1- and Th17-cell differentiation. Immunity 2007, 26:579-591.
56. Powrie F., Carlino J., Leach M.W., Mauze S., Coffman R.L. A critical role for transforming growth factor-beta but not interleukin 4 in the suppression of T helper type 1-mediated colitis by CD45RB(low) CD4+ T cells. J Exp Med 1996, 183:2669-2674.
57. Kitani A., Fuss I.J., Nakamura K., Schwartz O.M., Usui T., Strober W. Treatment of experimental (trinitrobenzene sulfonic acid) colitis by intranasal administration of transforming growth factor (TGF)-beta1 plasmid: TGF-beta1-mediated suppression of T helper cell type 1 response occurs by interleukin (IL)-10 induction and IL-12 receptor beta2 chain downregulation. J Exp Med 2000, 192:41-52.
58. Di Sabatino A., Pickard K.M., Rampton D., Kruidenier L., Rovedatti L., Leakey N.A., et al. Blockade of transforming growth factor beta upregulates T-box transcription factor T-bet, and increases T helper cell type 1 cytokine and matrix metalloproteinase-3 production in the human gut mucosa. Gut 2008, 57:605-612.
59. Monteleone G., Del Vecchio Blanco G., Monteleone I., Fina D., Caruso R., Gioia V., et al. Post-transcriptional regulation of Smad7 in the gut of patients with inflammatory bowel disease. Gastroenterology 2005, 129:1420-1429.
60. Das L.M., Torres-Castillo M.D., Gill T., Levine A.D. TGF-beta conditions intestinal T cells to express increased levels of miR-155, associated with down-regulation of IL-2 and itk mRNA. Mucosal Immunol 2013, 6:167-176.
61. Yang X.O., Pappu B.P., Nurieva R., Akimzhanov A., Kang H.S., Chung Y., et al. T helper 17 lineage differentiation is programmed by orphan nuclear receptors ROR alpha and ROR gamma. Immunity 2008, 28:29-39.
62. Lee Y.K., Turner H., Maynard C.L., Oliver J.R., Chen D., Elson C.O., et al. Late developmental plasticity in the T helper 17 lineage. Immunity 2009, 30:92-107.
63. Das J., Ren G., Zhang L., Roberts A.I., Zhao X., Bothwell A.L., et al. Transforming growth factor beta is dispensable for the molecular orchestration of Th17 cell differentiation. J Exp Med 2009, 206:2407-2416.
64. McGeachy M.J., Bak-Jensen K.S., Chen Y., Tato C.M., Blumenschein W., McClanahan T., et al. TGF-beta and IL-6 drive the production of IL-17 and IL-10 by T cells and restrain T(H)-17 cell-mediated pathology. Nat Immunol 2007, 8:1390-1397.
65. Cerutti A., Rescigno M. The biology of intestinal immunoglobulin A responses. Immunity 2008, 28:740-750.
66. Cong Y., Feng T., Fujihashi K., Schoeb T.R., Elson C.O. A dominant, coordinated T regulatory cell-IgA response to the intestinal microbiota. Proc Natl Acad Sci USA 2009, 106:19256-19261.
67. Li R., Rosendahl A., Brodin G., Cheng A.M., Ahgren A., Sundquist C., et al. Deletion of exon I of SMAD7 in mice results in altered B cell responses. J Immunol 2006, 176:6777-6784.
68. Klein J., Ju W., Heyer J., Wittek B., Haneke T., Knaus P., et al. B cell-specific deficiency for Smad2 in vivo leads to defects in TGF-beta-directed IgA switching and changes in B cell fate. J Immunol 2006, 176:2389-2396.
69. Cazac B.B., Roes J. TGF-beta receptor controls B cell responsiveness and induction of IgA in vivo. Immunity 2000, 13:443-451.
70. Watanabe K., Sugai M., Nambu Y., Osato M., Hayashi T., Kawaguchi M., et al. Requirement for Runx proteins in IgA class switching acting downstream of TGF-beta 1 and retinoic acid signaling. J Immunol 2010, 184:2785-2792.
71. Seo G.Y., Jang Y.S., Kim H.A., Lee M.R., Park M.H., Park S.R., et al. Retinoic acid, acting as a highly specific IgA isotype switch factor, cooperates with TGF-β1 to enhance the overall IgA response. J Leukoc Biol 2013, 94:325-335.
72. Tezuka H., Abe Y., Iwata M., Takeuchi H., Ishikawa H., Matsushita M., et al. Regulation of IgA production by naturally occurring TNF/iNOS-producing dendritic cells. Nature 2007, 448:929-933.
73. Biancheri P., Di Sabatino A., Corazza G.R., MacDonald T.T. Proteases and the gut barrier. Cell Tissue Res 2013, 351:269-280.
74. Sorokin L. The impact of the extracellular matrix on inflammation. Nat Rev Immunol 2010, 10:712-723.
75. Salmela M.T., Pender S.L., Karjalainen-Lindsberg M.L., Puolakkainen P., Macdonald T.T., Saarialho-Kere U. Collagenase-1 (MMP-1), matrilysin-1 (MMP-7), and stromelysin-2 (MMP-10) are expressed by migrating enterocytes during intestinal wound healing. Scand J Gastroenterol 2004, 39:1095-1104.
76. Ciacci C., Lind S.E., Podolsky D.K. Transforming growth factor beta regulation of migration in wounded rat intestinal epithelial monolayers. Gastroenterology 1993, 105:93-101.
77. McKaig B.C., Hughes K., Tighe P.J., Mahida Y.R. Differential expression of TGF-beta isoforms by normal and inflammatory bowel disease intestinal myofibroblasts. Am J Physiol Cell Physiol 2002, 282:C172-C182.
78. Dignass A.U., Podolsky D.K. Cytokine modulation of intestinal epithelial cell restitution: central role of transforming growth factor beta. Gastroenterology 1993, 105:1323-1332.
79. Yamada Y., Mashima H., Sakai T., Matsuhashi T., Jin M., Ohnishi H. Functional roles of TGF-β1 in intestinal epithelial cells through Smad-dependent and non-Smad pathways. Dig Dis Sci 2013, 58:1207-1217.
80. Guzik K., Potempa J. Friendly fire against neutrophils: proteolytic enzymes confuse the recognition of apoptotic cells by macrophages. Biochimie 2008, 90:405-415.
81. Fadok V.A., Bratton D.L., Konowal A., Freed P.W., Westcott J.Y., Henson P.M. Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-beta, PGE2, and PAF. J Clin Invest 1998, 101:890-898.
82. McDonald P.P., Fadok V.A., Bratton D., Henson P.M. Transcriptional and translational regulation of inflammatory mediator production by endogenous TGF-beta in macrophages that have ingested apoptotic cells. J Immunol 1999, 163:6164-6172.
83. Hinz B., Phan S.H., Thannickal V.J., Prunotto M., Desmouliere A., Varga J., et al. Recent developments in myofibroblast biology: paradigms for connective tissue remodeling. Am J Pathol 2012, 180:1340-1355.
84. Wipff P.J., Rifkin D.B., Meister J.J., Hinz B. Myofibroblast contraction activates latent TGF-beta1 from the extracellular matrix. J Cell Biol 2007, 179:1311-1323.
85. Wells R.G., Discher D.E. Matrix elasticity, cytoskeletal tension, and TGF-beta: the insoluble and soluble meet. Sci Signal 2008, 1:pe13.
86. Peters T., Sindrilaru A., Hinz B., Hinrichs R., Menke A., Al-Azzeh E.A., et al. Wound-healing defect of CD18(-/-) mice due to a decrease in TGF-beta1 and myofibroblast differentiation. EMBO J 2005, 24:3400-3410.
87. McKaig B.C., Makh S.S., Hawkey C.J., Podolsky D.K., Mahida Y.R. Normal human colonic subepithelial myofibroblasts enhance epithelial migration (restitution) via TGF-beta3. Am J Physiol 1999, 276:G1087-G1093.
88. Gabbiani G. The myofibroblast in wound healing and fibrocontractive diseases. J Pathol 2003, 200:500-503.
89. Vaday G.G., Schor H., Rahat M.A., Lahat N., Lider O. Transforming growth factor-beta suppresses tumor necrosis factor alpha-induced matrix metalloproteinase-9 expression in monocytes. J Leukoc Biol 2001, 69:613-621.
90. Boirivant M., Pallone F., Di Giacinto C., Fina D., Monteleone I., Marinaro M., et al. Inhibition of Smad7 with a specific antisense oligonucleotide facilitates TGF-beta1-mediated suppression of colitis. Gastroenterology 2006, 131:1786-1798.
91. Neurath M.F., Fuss I., Kelsall B.L., Presky D.H., Waegell W., Strober W. Experimental granulomatous colitis in mice is abrogated by induction of TGF-beta-mediated oral tolerance. J Exp Med 1996, 183:2605-2616.
92. Laffont S., Siddiqui K.R., Powrie F. Intestinal inflammation abrogates the tolerogenic properties of MLN CD103+ dendritic cells. Eur J Immunol 2010, 40:1877-1883.
93. Rizzo A., Waldner M.J., Stolfi C., Sarra M., Fina D., Becker C., et al. Smad7 expression in T cells prevents colitis-associated cancer. Cancer Res 2011, 71:7423-7432.
94. Fantini M.C., Becker C., Tubbe I., Nikolaev A., Lehr H.A., Galle P., et al. Transforming growth factor beta induced FoxP3+ regulatory T cells suppress Th1 mediated experimental colitis. Gut 2006, 55:671-680.
95. Becker C., Fantini M.C., Neurath M.F. TGF-beta as a T cell regulator in colitis and colon cancer. Cytokine Growth Factor Rev 2006, 17:97-106.
96. Lawrance I.C., Wu F., Leite A.Z., Willis J., West G.A., Fiocchi C., et al. A murine model of chronic inflammation-induced intestinal fibrosis down-regulated by antisense NF-kappa B. Gastroenterology 2003, 125:1750-1761.
97. Ma Y., Guan Q., Bai A., Weiss C.R., Hillman C.L., Ma A., et al. Targeting TGF-beta1 by employing a vaccine ameliorates fibrosis in a mouse model of chronic colitis. Inflamm Bowel Dis 2010, 16:1040-1050.
98. Vallance B.A., Gunawan M.I., Hewlett B., Bercik P., Van Kampen C., Galeazzi F., et al. TGF-beta1 gene transfer to the mouse colon leads to intestinal fibrosis. Am J Physiol Gastrointest Liver Physiol 2005, 289:G116-G128.
99. Baumgart D.C., Sandborn W.J. Crohn's disease. Lancet 2012, 380:1590-1605.
100. Ordás I., Eckmann L., Talamini M., Baumgart D.C., Sandborn W.J. Ulcerative colitis. Lancet 2012, 380:1606-1619.
101. MacDonald T.T., Monteleone G. Immunity, inflammation, and allergy in the gut. Science 2005, 307:1920-1925.
102. Di Sabatino A., Biancheri P., Rovedatti L., MacDonald T.T., Corazza G.R. New pathogenic paradigms in inflammatory bowel disease. Inflamm Bowel Dis 2012, 18:368-371.
103. Monteleone G., Neurath M.F., MacDonald T.T. Inflammatory Bowel Disease. Principles of Mucosal Immunology 2012, 473-487. Garland Science/Taylor & Francis Group, London/New York. P.D. Smith, T.T. MacDonald, R.S. Blumberg (Eds.).
104. Babyatsky M.W., Rossiter G., Podolsky D.K. Expression of transforming growth factors alpha and beta in colonic mucosa in inflammatory bowel disease. Gastroenterology 1996, 110:975-984.
105. Monteleone G., Kumberova A., Croft N.M., McKenzie C., Steer H.W., MacDonald T.T. Blocking Smad7 restores TGF-beta1 signaling in chronic inflammatory bowel disease. J Clin Invest 2001, 108:601-609.
106. Monteleone G., Del Vecchio Blanco G., Palmieri G., Vavassori P., Monteleone I., Colantoni A., et al. Induction and regulation of Smad7 in the gastric mucosa of patients with Helicobacter pylori infection. Gastroenterology 2004, 126:674-682.
107. Maul J., Loddenkemper C., Mundt P., Berg E., Giese T., Stallmach A., et al. Peripheral and intestinal regulatory CD4+ CD25(high) T cells in inflammatory bowel disease. Gastroenterology 2005, 128:1868-1878.
108. Saruta M., Yu Q.T., Fleshner P.R., Mantel P.Y., Schmidt-Weber C.B., Banham A.H., et al. Characterization of FOXP3+CD4+ regulatory T cells in Crohn's disease. Clin Immunol 2007, 125:281-290.
109. Fantini M.C., Rizzo A., Fina D., Caruso R., Sarra M., Stolfi C., et al. Smad7 controls resistance of colitogenic T cells to regulatory T cell-mediated suppression. Gastroenterology 2009, 136:1308-1316.
110. MacDonald T.T., Bell I., Monteleone G. The opposing roles of IL-21 and TGFβ1 in chronic inflammatory bowel disease. Biochem Soc Trans 2011, 39:1061-1066.
111. MacDonald T.T., Monteleone I., Fantini M.C., Monteleone G. Regulation of homeostasis and inflammation in the intestine. Gastroenterology 2011, 140:1768-1775.
112. Hovhannisyan Z., Treatman J., Littman D.R., Mayer L. Characterization of interleukin-17-producing regulatory T cells in inflamed intestinal mucosa from patients with inflammatory bowel diseases. Gastroenterology 2011, 140:957-965.
113. Burke J.P., Mulsow J.J., O'Keane C., Docherty N.G., Watson R.W., O'Connell P.R. Fibrogenesis in Crohn's disease. Am J Gastroenterol 2007, 102:439-448.
114. Rieder F., Lawrance I.C., Leite A., Sans M. Predictors of fibrostenotic Crohn's disease. Inflamm Bowel Dis 2011, 17:2000-2007.
115. Di Sabatino A., Jackson C.L., Pickard K.M., Buckley M., Rovedatti L., Leakey N.A., et al. Transforming growth factor beta signalling and matrix metalloproteinases in the mucosa overlying Crohn's disease strictures. Gut 2009, 58:777-789.
116. Graham M.F., Diegelmann R.F., Elson C.O., Lindblad W.J., Gotschalk N., Gay S., et al. Collagen content and types in the intestinal strictures of Crohn's disease. Gastroenterology 1988, 94:257-265.
117. Stallmach A., Schuppan D., Riese H.H., Matthes H., Riecken E.O. Increased collagen type III synthesis by fibroblasts isolated from strictures of patients with Crohn's disease. Gastroenterology 1992, 102:1920-1929.
118. McKaig B.C., McWilliams D., Watson S.A., Mahida Y.R. Expression and regulation of tissue inhibitor of metalloproteinase-1 and matrix metalloproteinases by intestinal myofibroblasts in inflammatory bowel disease. Am J Pathol 2003, 162:1355-1360.
119. Di Sabatino A., Corazza G.R. Coeliac disease. Lancet 2009, 373:1480-1493.
120. Meresse B., Ripoche J., Heyman M., Cerf-Bensussan N. Celiac disease: from oral tolerance to intestinal inflammation, autoimmunity and lymphomagenesis. Mucosal Immunol 2009, 2:8-23.
121. Monteleone I., Sarra M., Del Vecchio Blanco G., Paoluzi O.A., Franzè E., Fina D., et al. Characterization of IL-17A-producing cells in celiac disease mucosa. J Immunol 2010, 184:2211-2218.
122. Hansson T., Ulfgren A.K., Lindroos E., Dann A.A., Dahlbom I., Klareskog L. Transforming growth factor-beta (TGF-beta) and tissue transglutaminase expression in the small intestine in children with coeliac disease. Scand J Immunol 2002, 56:530-537.
123. Nunes I., Gleizes P.E., Metz C.N., Rifkin D.B. Latent transforming growth factor-beta binding protein domains involved in activation and transglutaminase-dependent cross-linking of latent transforming growth factor-beta. J Cell Biol 1997, 136:1151-1163.
124. Halttunen T., Maki M. Serum immunoglobulin A from patients with celiac disease inhibits human T84 intestinal crypt epithelial cell differentiation. Gastroenterology 1999, 116:566-572.
125. Lahat N., Shapiro S., Karban A., Gerstein R., Kinarty A., Lerner A. Cytokine profile in coeliac disease. Scand J Immunol 1999, 49:441-446.
126. Lionetti P., Pazzaglia A., Moriondo M., Azzari C., Resti M., Amorosi A., et al. Differing patterns of transforming growth factor-beta expression in normal intestinal mucosa and in active celiac disease. J Pediatr Gastroenterol Nutr 1999, 29:308-313.
127. Forsberg G., Hernell O., Hammarström S., Hammarström M.L. Concomitant increase of IL-10 and pro-inflammatory cytokines in intraepithelial lymphocyte subsets in celiac disease. Int Immunol 2007, 19:993-1001.
128. Fernandez S., Molina I.J., Romero P., Gonzalez R., Pena J., Sanchez F., et al. Characterization of gliadin-specific Th17 cells from the mucosa of celiac disease patients. Am J Gastroenterol 2011, 106:528-538.
129. Di Sabatino A., Ciccocioppo R., Cupelli F., Cinque B., Millimaggi D., Clarkson M.M., et al. Epithelium derived interleukin 15 regulates intraepithelial lymphocyte Th1 cytokine production, cytotoxicity, and survival in coeliac disease. Gut 2006, 55:469-477.
130. Di Sabatino A., Calarota S.A., Vidali F., Macdonald T.T., Corazza G.R. Role of IL-15 in immune-mediated and infectious diseases. Cytokine Growth Factor Rev 2011, 22:19-33.
131. Bhagat G., Naiyer A.J., Shah J.G., Harper J., Jabri B., Wang T.C., et al. Small intestinal CD8+TCRgammadelta+NKG2A+ intraepithelial lymphocytes have attributes of regulatory cells in patients with celiac disease. J Clin Invest 2008, 118:281-293.
132. Kagnoff M.F. Mucosal inflammation in celiac disease: interleukin-15 meets transforming growth factor beta-1. Gastroenterology 2007, 132:1174-1176.
133. Monteleone G., Boirivant M., Pallone F., MacDonald T.T. TGF-beta1 and Smad7 in the regulation of IBD. Mucosal Immunol 2008, 1(Suppl 1):S50-S53.
134. Monteleone G., Caruso R., Pallone F. Role of Smad7 in inflammatory bowel diseases. World J Gastroenterol 2012, 18:5664-5668.
135. Zorzi F., Angelucci E., Sedda S., Pallone F., Monteleone G. Smad7 antisense oligonucleotide-based therapy for inflammatory bowel diseases. Dig Liver Dis 2013, 45:552-555.
136. Fina D., Franzè E., Rovedatti L., Corazza G.R., Biancone L., Sileri P.P., et al. Interleukin-25 production is differently regulated by TNF-α and TGF-β1 in the human gut. Mucosal Immunol 2011, 4:239-244.
137. Caruso R., Sarra M., Stolfi C., Rizzo A., Fina D., Fantini M.C., et al. Interleukin-25 inhibits interleukin-12 production and Th1 cell-driven inflammation in the gut. Gastroenterology 2009, 136:2270-2279.
138. Monteleone I., Federici M., Sarra M., Franzè E., Casagrande V., Zorzi F., et al. Tissue inhibitor of metalloproteinase-3 regulates inflammation in human and mouse intestine. Gastroenterology 2012, 143:1277-1287.
139. Monteleone G., Fantini M.C., Onali S., Zorzi F., Sancesario G., Bernardini S., et al. Phase I clinical trial of Smad7 knockdown using antisense oligonucleotide in patients with active Crohn's disease. Mol Ther 2012, 20:870-876.
140. Zorzi F., Calabrese E., Monteleone I., Fantini M., Onali S., Biancone L., et al. A phase 1 open-label trial shows that smad7 antisense oligonucleotide (GED0301) does not increase the risk of small bowel strictures in Crohn's disease. Aliment Pharmacol Ther 2012, 36:850-857.
141. Marafini I., Zorzi F., Codazza S., Pallone F., Monteleone G. TGF-beta signaling manipulation as potential therapy for IBD. Curr Drug Targets 2013, 14:1400-1404.
142. Latella G., Vetuschi A., Sferra R., Zanninelli G., D'Angelo A., Catitti V., et al. Smad3 loss confers resistance to the development of trinitrobenzene sulfonic acid-induced colorectal fibrosis. Eur J Clin Invest 2009, 39:145-156.
143. Latella G., Sferra R., Vetuschi A., Zanninelli G., D'Angelo A., Catitti V., et al. Prevention of colonic fibrosis by Boswellia and Scutellaria extracts in rats with colitis induced by 2,4,5-trinitrobenzene sulphonic acid. Eur J Clin Invest 2008, 38:410-420.
144. Latella G., Sferra R., Speca S., Vetuschi A., Gaudio E. Can we prevent, reduce or reverse intestinal fibrosis in IBD. Eur Rev Med Pharmacol Sci 2013, 17:1283-1304.
145. Speca S., Rousseaux C., Dubuquoy C., Vetuschi A., Sferra R., Bertin B., et al. GED-0507 34 Levo, a novel modulator of PPARgamma as new therapeutic strategy in the treatment of intestinal fibrosis. J Crohns Colitis 2013, 7(Suppl 1):S31-S32.
146. Wengrower D., Zanninelli G., Pappo O., Latella G., Sestieri M., Villanova A., et al. Prevention of fibrosis in experimental colitis by captopril: the role of tgf-beta1. Inflamm Bowel Dis 2004, 10:536-545.
147. Koga H., Yang H., Adler J., Zimmermann E.M., Teitelbaum D.H. Transanal delivery of angiotensin converting enzyme inhibitor prevents colonic fibrosis in a mouse colitis model: development of a unique mode of treatment. Surgery 2008, 144:259-268.
148. Wengrower D., Zanninelli G., Latella G., Necozione S., Metanes I., Israeli E., et al. Losartan reduces trinitrobenzene sulphonic acid-induced colorectal fibrosis in rats. Can J Gastroenterol 2012, 26:33-39.
149. Schuppan D., Pinzani M. Anti-fibrotic therapy: lost in translation?. J Hepatol 2012, 56(Suppl 1):S66-S74.