Intestinal epithelial expression of TNFAIP3 results in microbial invasion of the inner mucus layer and induces colitis in IL-10-deficient mice

American Journal of Physiology - Gastrointestinal and Liver Physiology

Volumn 307, Issue 9, 2014, Pages G871-G882

  Murphy, Stephen F ^a   Rhee, Lesley ^a   Grimm, Wesley A ^a   Weber, Christopher R ^a   Messer, Jeannette S ^a   Lodolce, James P ^a   Chang, Jonathan E ^a   Bartulis, Sarah J ^a   Nero, Thomas ^a   Kukla, Renata A ^a   MacDougall, Gordon ^b   Binghay, Charles ^b   Kolodziej, Lauren E ^a   Boone, David L ^b  

^a UNIVERSITY OF CHICAGO   (United States)

^b INDIANA UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

A20; Ang4; Intestinal mucus; NK B; Reg3

Indexed keywords

CXCL9 CHEMOKINE; GAMMA INTERFERON; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 10; INTERLEUKIN 4; PANCREATIC LIPASE RELATED PROTEIN 2; PROTEIN; TUMOR NECROSIS FACTOR INDUCED PROTEIN 3; UNCLASSIFIED DRUG; URIDINE PHOSPHORYLASE 1; ANG4 PROTEIN, MOUSE; CYSTEINE PROTEINASE; IL10 PROTEIN, MOUSE; LECTIN; PANCREATIC RIBONUCLEASE; PANCREATITIS-ASSOCIATED PROTEIN; SIGNAL PEPTIDE; TNFAIP3 PROTEIN, MOUSE; TUMOR ANTIGEN; TUMOR MARKER;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BACTERIAL LOAD; CELL INFILTRATION; CELL SURFACE; COLITIS; COLON MUCOSA; CONTROLLED STUDY; DISEASE SEVERITY; ENZYME LINKED IMMUNOSORBENT ASSAY; FLOW CYTOMETRY; FLUORESCENCE IN SITU HYBRIDIZATION; GENE EXPRESSION; HISTOPATHOLOGY; IMMUNOBLOTTING; IMMUNOCOMPETENT CELL; IMMUNOHISTOCHEMISTRY; INFLAMMATORY BOWEL DISEASE; INTESTINE EPITHELIUM CELL; MICROARRAY ANALYSIS; MICROBIAL COLONIZATION; MICROBIOME; MOUSE; NONHUMAN; ONSET AGE; PROTEIN EXPRESSION; REGULATORY T LYMPHOCYTE; ANIMAL; C57BL MOUSE; GENE DELETION; GENETICS; INTESTINE MUCOSA; METABOLISM; MICROBIOLOGY; MICROFLORA; PATHOLOGY; ULCERATIVE COLITIS;

ANIMALS; ANTIGENS, NEOPLASM; COLITIS, ULCERATIVE; CYSTEINE ENDOPEPTIDASES; GENE DELETION; INTERLEUKIN-10; INTESTINAL MUCOSA; INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS; LECTINS, C-TYPE; MICE; MICE, INBRED C57BL; MICROBIOTA; RIBONUCLEASE, PANCREATIC; TUMOR MARKERS, BIOLOGICAL;

EID: 84908377619     PISSN: 01931857     EISSN: 15221547     Source Type: Journal    
DOI: 10.1152/ajpgi.00020.2014     Document Type: Article

References (41)

1. Arsenescu R, Bruno ME, Rogier EW, Stefka AT, McMahan AE, Wright TB, Nasser MS, de Villiers WJ, Kaetzel CS. Signature biomarkers in Crohn's disease: toward a molecular classification. Mucosal Immunol 1: 399-411, 2008.
2. Boone DL, Turer EE, Lee EG, Ahmad RC, Wheeler MT, Tsui C, Hurley P, Chien M, Chai S, Hitotsumatsu O, McNally E, Pickart C, Ma A. The ubiquitin-modifying enzyme A20 is required for termination of Toll-like receptor responses. Nat Immunol 5: 1052-1060, 2004.
3. Catrysse L, Vereecke L, Beyaert R, van Loo G. A20 in inflammation and autoimmunity. Trends Immunol 35: 22-31, 2014.
4. Compagno M, Lim WK, Grunn A, Nandula SV, Brahmachary M, Shen Q, Bertoni F, Ponzoni M, Scandurra M, Califano A, Bhagat G, Chadburn A, Dalla-Favera R, Pasqualucci L. Mutations of multiple genes cause deregulation of NF-kappaB in diffuse large B-cell lymphoma. Nature 459: 717-721, 2009.
5. Davidson NJ, Leach MW, Fort MM, Thompson-Snipes L, Kuhn R, Muller W, Berg DJ, Rennick DM. T helper cell 1-type CD4+ T cells, but not B cells, mediate colitis in interleukin 10-deficient mice. J Exp Med 184: 241-251, 1996.
6. Devkota S, Chang EB. Diet-induced expansion of pathobionts in experimental colitis: implications for tailored therapies. Gut Microbes 4: 172- 174, 2013.
7. Eckmann L, Nebelsiek T, Fingerle AA, Dann SM, Mages J, Lang R, Robine S, Kagnoff MF, Schmid RM, Karin M, Arkan MC, Greten FR. Opposing functions of IKKbeta during acute and chronic intestinal inflammation. Proc Natl Acad Sci USA 105: 15058-15063, 2008.
8. Edelblum KL, Yan F, Yamaoka T, Polk DB. Regulation of apoptosis during homeostasis and disease in the intestinal epithelium. Inflamm Bowel Dis 12: 413-424, 2006.
9. Frank DN, St Amand AL, Feldman RA, Boedeker EC, Harpaz N, Pace NR. Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proc Natl Acad Sci USA 104: 13780-13785, 2007.
10. Gallo RL, Hooper LV. Epithelial antimicrobial defence of the skin and intestine. Nat Rev Immunol 12: 503-516, 2012.
11. Garg AV, Ahmed M, Vallejo AN, Ma A, Gaffen SL. The deubiquitinase A20 mediates feedback inhibition of interleukin-17 receptor signaling. Sci Signal 6: ra44, 2013.
12. Hammer GE, Turer EE, Taylor KE, Fang CJ, Advincula R, Oshima S, Barrera J, Huang EJ, Hou B, Malynn BA, Reizis B, DeFranco A, Criswell LA, Nakamura MC, Ma A. Expression of A20 by dendritic cells preserves immune homeostasis and prevents colitis and spondyloarthritis. Nat Immunol 12: 1184-1193, 2011.
13. Hansen JJ, Holt L, Sartor RB. Gene expression patterns in experimental colitis in IL-10-deficient mice. Inflamm Bowel Dis 15: 890-899, 2009.
14. Hitotsumatsu O, Ahmad RC, Tavares R, Wang M, Philpott D, Turer EE, Lee BL, Shiffin N, Advincula R, Malynn BA, Werts C, Ma A. The ubiquitin-editing enzyme A20 restricts nucleotide-binding oligomerization domain containing 2-triggered signals. Immunity 28: 381-390, 2008.
15. Hooper LV, Stappenbeck TS, Hong CV, Gordon JI. Angiogenins: a new class of microbicidal proteins involved in innate immunity. Nat Immunol 4: 269-273, 2003.
16. Hymowitz SG, Wertz IE. A20: from ubiquitin editing to tumour suppression. Nat Rev Cancer 10: 332-341, 2010.
17. Johansson ME, Phillipson M, Petersson J, Velcich A, Holm L, Hansson GC. The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria. Proc Natl Acad Sci USA 105: 15064-15069, 2008.
18. Jostins L, Ripke S, Weersma RK, Duerr RH, McGovern DP, Hui KY, Lee JC, Schumm LP, Sharma Y, Anderson CA, Essers J, Mitrovic M, Ning K, Cleynen I, Theatre E, Spain SL, Raychaudhuri S, Goyette P, Wei Z, Abraham C, Achkar JP, Ahmad T, Amininejad L, Anan thakrishnan AN, Andersen V, Andrews JM, Baidoo L, Balschun T, Bampton PA, Bitton A, Boucher G, Brand S, Buning C, Cohain A, Cichon S, D'Amato M, De Jong D, Devaney KL, Dubinsky M, Edwards C, Ellinghaus D, Ferguson LR, Franchimont D, Fransen K, Gearry R, Georges M, Gieger C, Glas J, Haritunians T, Hart A, Hawkey C, Hedl M, Hu X, Karlsen TH, Kupcinskas L, Kugathasan S, Latiano A, Laukens D, Lawrance IC, Lees CW, Louis E, Mahy G, Mansfield J, Morgan AR, Mowat C, Newman W, Palmieri O, Ponsioen CY, Potocnik U, Prescott NJ, Regueiro M, Rotter JI, Russell RK, Sanderson JD, Sans M, Satsangi J, Schreiber S, Simms LA, Sventoraityte J, Targan SR, Taylor KD, Tremelling M, Verspaget HW, De Vos M, Wijmenga C, Wilson DC, Winkelmann J, Xavier RJ, Zeissig S, Zhang B, Zhang CK, Zhao H, International IBD Genetics Consortium, Silverberg MS, Annese V, Hakonarson H, Brant SR, Radford-Smith G, Mathew CG, Rioux JD, Schadt EE, Daly MJ, Franke A, Parkes M, Vermeire S, Barrett JC, Cho JH. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 491: 119-124, 2012.
19. Kato M, Sanada M, Kato I, Sato Y, Takita J, Takeuchi K, Niwa A, Chen Y, Nakazaki K, Nomoto J, Asakura Y, Muto S, Tamura A, Iio M, Akatsuka Y, Hayashi Y, Mori H, Igarashi T, Kurokawa M, Chiba S, Mori S, Ishikawa Y, Okamoto K, Tobinai K, Nakagama H, Nakahata T, Yoshino T, Kobayashi Y, Ogawa S. Frequent inactivation of A20 in B-cell lymphomas. Nature 459: 712-716, 2009.
20. Khounlotham M, Kim W, Peatman E, Nava P, Medina-Contreras O, Addis C, Koch S, Fournier B, Nusrat A, Denning TL, Parkos CA. Compromised intestinal epithelial barrier induces adaptive immune compensation that protects from colitis. Immunity 37: 563-573, 2012.
21. Kolodziej LE, Lodolce JP, Chang JE, Schneider JR, Grimm WA, Bartulis SJ, Zhu X, Messer JS, Murphy SF, Reddy N, Turner JR, Boone DL. TNFAIP3 maintains intestinal barrier function and supports epithelial cell tight junctions. PLoS One 6: e26352, 2011.
22. Kool M, van Loo G, Waelput W, De Prijck S, Muskens F, Sze M, van Praet J, Branco-Madeira F, Janssens S, Reizis B, Elewaut D, Beyaert R, Hammad H, Lambrecht BN. The ubiquitin-editing protein A20 prevents dendritic cell activation, recognition of apoptotic cells, and systemic autoimmunity. Immunity 35: 82-96, 2011.
23. Lee EG, Boone DL, Chai S, Libby SL, Chien M, Lodolce JP, Ma A. Failure to regulate TNF-induced NF-kappaB and cell death responses in A20-deficient mice. Science 289: 2350-2354, 2000.
24. Lippens S, Lefebvre S, Gilbert B, Sze M, Devos M, Verhelst K, Vereecke L, McGuire C, Guerin C, Vandenabeele P, Pasparakis M, Mikkola ML, Beyaert R, Declercq W, van Loo G. Keratinocyte-specific ablation of the NF-kappaB regulatory protein A20 (TNFAIP3) reveals a role in the control of epidermal homeostasis. Cell Death Diff 18: 1845- 1853, 2011.
25. Lodolce JP, Kolodziej LE, Rhee L, Kariuki SN, Franek BS, McGreal NM, Logsdon MF, Bartulis SJ, Perera MA, Ellis NA, Adams EJ, Hanauer SB, Jolly M, Niewold TB, Boone DL. African-derived genetic polymorphisms in TNFAIP3 mediate risk for autoimmunity. J Immunol 184: 7001-7009, 2010.
26. Ma A, Malynn BA. A20: linking a complex regulator of ubiquitylation to immunity and human disease. Nat Rev Immunol 12: 774-785, 2012.
27. Madsen KL, Malfair D, Gray D, Doyle JS, Jewell LD, Fedorak RN. Interleukin-10 gene-deficient mice develop a primary intestinal permeability defect in response to enteric microflora. Inflamm Bowel Dis 5: 262-270, 1999.
28. Matmati M, Jacques P, Maelfait J, Verheugen E, Kool M, Sze M, Geboes L, Louagie E, McGuire C, Vereecke L, Chu Y, Boon L, Staelens S, Matthys P, Lambrecht BN, Schmidt-Supprian M, Pasparakis M, Elewaut D, Beyaert R, van Loo G. A20 (TNFAIP3) deficiency in myeloid cells triggers erosive polyarthritis resembling rheumatoid arthritis. Nat Genet 43: 908-912, 2011.
29. Musone SL, Taylor KE, Lu TT, Nititham J, Ferreira RC, Ortmann W, Shifrin N, Petri MA, Kamboh MI, Manzi S, Seldin MF, Gregersen PK, Behrens TW, Ma A, Kwok PY, Criswell LA. Multiple polymorphisms in the TNFAIP3 region are independently associated with systemic lupus erythematosus. Nat Genet 40: 1062-1064, 2008.
30. Nava GM, Friedrichsen HJ, Stappenbeck TS. Spatial organization of intestinal microbiota in the mouse ascending colon. ISME J 5: 627-638, 2011.
31. Nenci A, Becker C, Wullaert A, Gareus R, van Loo G, Danese S, Huth M, Nikolaev A, Neufert C, Madison B, Gumucio D, Neurath MF, Pasparakis M. Epithelial NEMO links innate immunity to chronic intestinal inflammation. Nature 446: 557-561, 2007.
32. Otsuka M, Kang YJ, Ren J, Jiang H, Wang Y, Omata M, Han J. Distinct effects of p38alpha deletion in myeloid lineage and gut epithelia in mouse models of inflammatory bowel disease. Gastroenterology 138: 1255-1265; e1251-e1259, 2010.
33. Rhee L, Murphy SF, Kolodziej LE, Grimm WA, Weber CR, Lodolce JP, Chang JE, Bartulis SJ, Messer JS, Schneider JR, Paski S, Nero TM, Boone DL. Expression of TNFAIP3 in intestinal epithelial cells protects from DSS- but not TNBS-induced colitis. Am J Physiol Gastrointest Liver Physiol 303: G220-G227, 2012.
34. Sellon RK, Tonkonogy S, Schultz M, Dieleman LA, Grenther W, Balish E, Rennick DM, Sartor RB. Resident enteric bacteria are necessary for development of spontaneous colitis and immune system activation in interleukin-10-deficient mice. Infect Immun 66: 5224-5231, 1998.
35. Shao L, Oshima S, Duong B, Advincula R, Barrera J, Malynn BA, Ma A. A20 restricts Wnt signaling in intestinal epithelial cells and suppresses colon carcinogenesis. PLoS One 8: e62223, 2013.
36. Tavares RM, Turer EE, Liu CL, Advincula R, Scapini P, Rhee L, Barrera J, Lowell CA, Utz PJ, Malynn BA, Ma A. The ubiquitin modifying enzyme A20 restricts B cell survival and prevents autoimmunity. Immunity 33: 181-191, 2010.
37. Turer EE, Tavares RM, Mortier E, Hitotsumatsu O, Advincula R, Lee B, Shifrin N, Malynn BA, Ma A. Homeostatic MyD88-dependent signals cause lethal inflammation in the absence of A20. J Exp Med 205: 451-464, 2008.
38. Vereecke L, Sze M, McGuire C, Rogiers B, Chu Y, Schmidt-Supprian M, Pasparakis M, Beyaert R, van Loo G. Enterocyte-specific A20 deficiency sensitizes to tumor necrosis factor-induced toxicity and experimental colitis. J Exp Med 207: 1513-1523, 2010.
39. Wang J, Ouyang Y, Guner Y, Ford HR, Grishin AV. Ubiquitin-editing enzyme A20 promotes tolerance to lipopolysaccharide in enterocytes. J Immunol 183: 1384-1392, 2009.
40. Willson TA, Jurickova I, Collins M, Denson LA. Deletion of intestinal epithelial cell STAT3 promotes T-lymphocyte STAT3 activation and chronic colitis following acute dextran sodium sulfate injury in mice. Inflamm Bowel Dis 19: 512-525, 2013.
41. Zaph C, Troy AE, Taylor BC, Berman-Booty LD, Guild KJ, Du Y, Yost EA, Gruber AD, May MJ, Greten FR, Eckmann L, Karin M, Artis D. Epithelial-cell-intrinsic IKK-beta expression regulates intestinal immune homeostasis. Nature 446: 552-556, 2007.