Targeted epithelial tight junction dysfunction causes immune activation and contributes to development of experimental colitis
Open accessAbstract
Background & aims Inflammatory bowel disease (IBD) is a multifactorial disease thought to be caused by alterations in epithelial function, innate and adaptive immunity, and luminal microbiota. The specific role of epithelial barrier function remains undefined, although increased activity of intestinal epithelial myosin light chain kinase (MLCK), which is the primary mechanism of tumor necrosis factor-induced barrier dysfunction, occurs in human IBD. Our aim was to determine whether, in an intact epithelium, primary dysregulation of the intestinal epithelial barrier by pathophysiologically relevant mechanisms can contribute to development of colitis.Methods We developed transgenic (Tg) mice that express constitutively active MLCK (CA-MLCK) specifically within intestinal epithelia. Their physiology, immune status, and susceptibility to disease were assessed and compared with non-Tg littermate controls.Results CA-MLCK Tg mice demonstrated significant barrier loss but grew and gained weight normally and did not develop spontaneous disease. CA-MLCK Tg mice did, however, develop mucosal immune activation demonstrated by increased numbers of lamina propria CD4(+)lymphocytes, redistribution of CD11c+cells, increased production of interferon-gamma and tumor necrosis factor, as well as increased expression of epithelial major histocompatibility complex class I. When challenged with CD4+CD45+Rb(hi) lymphocytes, Tg mice developed an accelerated and more severe form of colitis and had shorter survival times than non-Tg littermates.Conclusions Primary pathophysiologically relevant intestinal epithelial barrier dysfunction is insufficient to cause experimental intestinal disease but can broadly activate mucosal immune responses and accelerate the onset and severity of immune-mediated colitis.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The leak pathway is believed to be regulated by myosin light-chain kinase, where constitutively active MLCK is sufficient to increase the leak pathway-dependent permeability both in vitro and in vivo.
“The leak pathway is believed to be regulated by myosin light-chain kinase (MLCK), where constitutively active MLCK is sufficient to increase the leak pathway–dependent permeability both in vitro and in vivo.52,53”
From Regulation of Intestinal Barrier Function by Microbial Metabolites (2021) · cites this paper as [53]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Clinicopathologic study of dextran sulfate sodium experimental acute colitis
Shichijo, K., Matuu, M., Ikeda, Y., Naito, S., Ito, M., & Sekine, I. (1998) · The Japanese Journal of Pharmacology · doi:10.1016/s0021-5198(19)41298-5 · Cited by 1,943 · see citing works
Microbial Influences in Inflammatory Bowel Diseases
Sartor, R. B. (2008) · Gastroenterology · doi:10.1053/j.gastro.2007.11.059 · Cited by 1,927 · see citing works
Zeißig, S., Bürgel, N., Günzel, D., Richter, J. F., Mankertz, J., Wahnschaffe, U., Kroesen, A. J., Zeitz, M., Fromm, M., & Schulzke, J. (2006) · Gut · doi:10.1136/gut.2006.094375 · Cited by 1,218 · see citing works
Powrie, F., Leach, M. W., Mauze, S., Menon, S., Barcomb Caddle, L., & Coffman, R. L. (1994) · Immunity · doi:10.1016/1074-7613(94)90045-0 · Cited by 1,146 · see citing works
Cutting Edge: Cure of Colitis by CD4+CD25+ Regulatory T Cells
Mottet, C., Uhlig, H. H., & Powrie, F. M. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.170.8.3939 · Cited by 928 · see citing works
Increased Intestinal Permeability in Patients with Crohn's Disease and Their Relatives
Hollander, D., Vadheim, C. M., Brettholz, E., Petersen, G. M., Delahunty, T., & Rotter, J. I. (1986) · Annals of Internal Medicine · doi:10.7326/0003-4819-105-6-883 · Cited by 762 · see citing works
Inflammatory Bowel Disease and Adenomas in Mice Expressing a Dominant Negative N-Cadherin
Hermiston, M. L., & Gordon, J. I. (1995) · Science · doi:10.1126/science.270.5239.1203 · Cited by 669 · see citing works
Intestinal permeability and the prediction of relapse in Crohn's disease
Wyatt, J., Vogelsang, H., Hübl, W., Waldhoer, T., & Lochs, H. (1993) · The Lancet · doi:10.1016/0140-6736(93)90882-h · Cited by 626 · see citing works
Turner, J. R., Rill, B. K., Carlson, S. L., Carnes, D., Kerner, R., Mrsny, R. J., & Madara, J. (1997) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1997.273.4.c1378 · Cited by 553 · see citing works
A porous defense: the leaky epithelial barrier in intestinal disease
Clayburgh, D. R., Shen, L., & Turner, J. R. (2004) · Laboratory Investigation · doi:10.1038/labinvest.3700050 · Cited by 496 · see citing works
Myosin light chain phosphorylation regulates barrier function by remodeling tight junction structure
Shen, L., Black, E. D., Witkowski, E. D., Lencer, W. I., Guerriero, V., Schneeberger, E. E., & Turner, J. R. (2006) · Journal of Cell Science · doi:10.1242/jcs.02915 · Cited by 467 · see citing works
Clayburgh, D. R. (2005) · Journal of Clinical Investigation · doi:10.1172/jci24970 · Cited by 419 · see citing works
Hermiston, M. L., & Gordon, J. I. (1995) · The Journal of Cell Biology · doi:10.1083/jcb.129.2.489 · Cited by 415 · see citing works
Zolotarevsky, Y., Hecht, G. A., Koutsouris, A., Gonzalez, D. E., Quan, C., Tom, J., Mrsny, R. J., & Turner, J. R. (2002) · Gastroenterology · doi:10.1053/gast.2002.34235 · Cited by 385 · see citing works
Madsen, K. L., Malfair, D., Gray, D., Doyle, J. S. G., Jewell, L. D., & Fedorak, R. N. (1999) · Inflammatory Bowel Diseases · doi:10.1097/00054725-199911000-00004 · Cited by 318 · see citing works
Is small intestinal permeability really increased in relatives of patients with Crohn's disease?
May, G. R., Sutherland, L. R., & Meddings, J. B. (1993) · Gastroenterology · doi:10.1016/0016-5085(93)90638-s · Cited by 316 · see citing works
Intestinal permeability in patients with Crohn's disease and their healthy relatives
Katz, K. D., Hollander, D., Vadheim, C. M., McElree, C. K., Delahunty, T., Dadufalza, V. D., Krugliak, P., & Rotter, J. I. (1989) · Gastroenterology · doi:10.1016/0016-5085(89)91499-6 · Cited by 302 · see citing works
Blair, S. A., Kane, S. V., Clayburgh, D. R., & Turner, J. R. (2006) · Laboratory Investigation · doi:10.1038/labinvest.3700373 · Cited by 298 · see citing works
Irvine, E. J., & Marshall, J. K. (2000) · Gastroenterology · doi:10.1053/gast.2000.20231 · Cited by 286 · see citing works
A comparative analysis of two models of colitis in rats
Yamada, T., Marshall, S. J., Specian, R. D., & Grisham, M. B. (1992) · Gastroenterology · doi:10.1016/0016-5085(92)91710-l · Cited by 264 · see citing works
Vetrano, S., Rescigno, M., Cera, M. R., Correale, C., Rumio, C., Doni, A., Fantini, M. C., Sturm, A., Borroni, E. M., Repici, A., et al. (2008) · Gastroenterology · doi:10.1053/j.gastro.2008.04.002 · Cited by 254 · see citing works
Intestinal permeability in children with Crohn's disease and coeliac disease.
Pearson, A., EASTHAM, E. J., Laker, M. F., Craft, A. W., & NELSON, R. L. (1982) · BMJ · doi:10.1136/bmj.285.6334.20 · Cited by 225 · see citing works
Intestinal Permeability Test As A Predictor of Clinical Course in Crohn's Disease
Renata D'Incà, Leo, V. D., Corrao, G., Martines, D., D’Odorico, A., Mestriner, C., Venturi, C., Longo, G., & Sturniolo, G. C. (1999) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.1999.01444.x · Cited by 218 · see citing works
Clayburgh, D. R., Musch, M. W., Leitges, M., Fu, Y., & Turner, J. R. (2006) · Journal of Clinical Investigation · doi:10.1172/jci29218 · Cited by 203 · see citing works
Epithelial permeability to proteins in the noninflamed ileum of Crohn's disease?
Söderholm, J. D., Peterson, K. H., Olaison, G., Franzén, L., Weström, B. R., Magnusson, K., & Sjödahl, R. I. (1999) · Gastroenterology · doi:10.1016/s0016-5085(99)70551-2 · Cited by 201 · see citing works
Discrimination of site-specific alterations in gastrointestinal permeability in the rat
Meddings, J. B., & Gibbons, I. (1998) · Gastroenterology · doi:10.1016/s0016-5085(98)70636-5 · Cited by 195 · see citing works
Intestinal permeability in patients with Crohn's disease and their first degree relatives.
Teahon, K., Smethurst, P., Levi, A. J., Menzies, I. S., & Bjarnason, I. (1992) · Gut · doi:10.1136/gut.33.3.320 · Cited by 195 · see citing works
The primary defect in experimental ileitis originates from a nonhematopoietic source
Olson, T. S., Reuter, B. K., Scott, K. G. –., MORRIS, M. A., Wang, X.-M., Hancock, L. N., Burcin, T. L., Cohn, S. M., Ernst, P. B., Cominelli, F., et al. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20050407 · Cited by 172 · see citing works
Pinto, D., Robine, S., Jaisser, F., Marjou, F. E., & Louvard, D. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.10.6476 · Cited by 134 · see citing works
Interferon-gamma induces a cell surface phenotype switch on T84 intestinal epithelial cells
Colgan, S. P., Parkos, C., Matthews, J. B., D'Andrea, L., Awtrey, C. S., Lichtman, A. H., Delp-Archer, C., & Madara, J. (1994) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1994.267.2.c402 · Cited by 134 · see citing works
Inflammatory bowel disease: is it really just another break in the wall?: Figure 1
Weber, C. R., & Turner, J. R. (2006) · Gut · doi:10.1136/gut.2006.104182 · Cited by 132 · see citing works
Resta‐Lenert, S. C., Smitham, J. E., & Barrett, K. E. (2005) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00395.2004 · Cited by 130 · see citing works
Fukata, M., Breglio, K. J., Chen, A., Vamadevan, A. S., Goo, T., Hsu, D. S., Conduah, D. E., Xu, R., & Abreu, M. T. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.3.1886 · Cited by 130 · see citing works
CD18 Is Required for Optimal Development and Function of CD4+CD25+ T Regulatory Cells
Marski, M., Kandula, S., Turner, J. R., & Abraham, C. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.12.7889 · Cited by 95 · see citing works
Boirivant, M., Amendola, A., Butera, A., Sanchez, M., Xu, L., Marinaro, M., Kitani, A., Giacinto, C. D., Strober, W., & Fuss, I. J. (2008) · Gastroenterology · doi:10.1053/j.gastro.2008.07.028 · Cited by 91 · see citing works
Turner, J. R., Cohen, D. E., Mrsny, R. J., & Madara, J. L. (2000) · Digestive Diseases and Sciences · doi:10.1023/a:1026682900586 · Cited by 74 · see citing works
Miki, K., Moore, D., Butler, R. N., Southcott, E., Couper, R. T. L., & Davidson, G. P. (1998) · The Journal of Pediatrics · doi:10.1016/s0022-3476(98)70145-3 · Cited by 70 · see citing works
Collett, A., Higgs, N. B., Gironella, M., Zeef, L. A. H., Hayes, A., Salmo, E., Haboubi, N. Y., Iovanna, J., Carlson, G., & Warhurst, G. (2008) · Inflammatory Bowel Diseases · doi:10.1002/ibd.20375 · Cited by 52 · see citing works
Madsen, K. L., Malfair, D., Gray, D., Doyle, J. S. G., Jewell, L. D., & Fedorak, R. N. (2007) · Inflammatory Bowel Diseases · doi:10.1002/ibd.3780050405 · Cited by 36 · see citing works
Silva, M. A., Porras, M., Jury, J., Vergara, P., & Perdue, M. H. (2006) · Inflammatory Bowel Diseases · doi:10.1097/00054725-200606000-00004 · Cited by 20 · see citing works
Pulimood, A. B., Ramakrishna, B., Rita, A. B., Srinivasan, P., Mohan, V., Gupta, S., Perakath, B., Kang, G., Chandy, G. M., & Balasubramanian, K. A. (2008) · Journal of Gastroenterology and Hepatology · doi:10.1111/j.1440-1746.2008.05325.x · Cited by 13 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Intestinal mucosal barrier function in health and disease
Turner, J. R. (2009) · Nature reviews. Immunology · doi:10.1038/nri2653 · Cited by 3,952 · see citing works
Intestinal epithelial cells: regulators of barrier function and immune homeostasis
Peterson, L. W., & Artis, D. (2014) · Nature reviews. Immunology · doi:10.1038/nri3608 · Cited by 3,191 · see citing works
Intestinal barrier function: molecular regulation and disease pathogenesis
Groschwitz, K. R., & Hogan, S. P. (2009) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2009.05.038 · Cited by 1,775 · see citing works
A gut bacterial pathway metabolizes aromatic amino acids into nine circulating metabolites
Dodd, D., Spitzer, M. H., Van Treuren, W., Merrill, B. D., Hryckowian, A. J., Higginbottom, S. K., Le, A., Cowan, T. M., Nolan, G. P., Fischbach, M. A., et al. (2017) · Nature · doi:10.1038/nature24661 · Cited by 1,425 · see citing works
The intestinal epithelial barrier: a therapeutic target?
Odenwald, M. A., & Turner, J. R. (2017) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2016.169 · Cited by 1,288 · see citing works
Intestinal barrier function in health and gastrointestinal disease
Camilleri, M., Madsen, K., Spiller, R., Van Meerveld, B. G., & Verne, G. N. (2012) · Neurogastroenterology & Motility · doi:10.1111/j.1365-2982.2012.01921.x · Cited by 908 · see citing works
Tight Junction Pore and Leak Pathways: A Dynamic Duo
Shen, L., Weber, C. R., Raleigh, D. R., Yu, D., & Turner, J. R. (2011) · Annual Review of Physiology · doi:10.1146/annurev-physiol-012110-142150 · Cited by 867 · see citing works
Regulation of Intestinal Barrier Function by Microbial Metabolites
Ghosh, S., Whitley, C. S., Haribabu, B., & Jala, V. R. (2021) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2021.02.007 · Cited by 835 · see citing works
Homeostasis and Inflammation in the Intestine
Garrett, W. S., Gordon, J. I., & Glimcher, L. H. (2010) · Cell · doi:10.1016/j.cell.2010.01.023 · Cited by 784 · see citing works
Cell Biology of Tight Junction Barrier Regulation and Mucosal DiseasePreprint
Buckley, A., & Turner, J. R. (2017) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a029314 · Cited by 725 · see citing works
Paracellular permeability and tight junction regulation in gut health and disease
Horowitz, A., Chánez-Paredes, S. D., Haest, X., & Turner, J. R. (2023) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-023-00766-3 · Cited by 725 · see citing works
Homeostasis of the gut barrier and potential biomarkers
Wells, J. M., Brummer, R. J., Derrien, M., MacDonald, T. T., Troost, F. J., Cani, P. D., Théodorou, V., Dekker, J. P., Méheust, A., de Vos, W. M., et al. (2016) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00048.2015 · Cited by 616 · see citing works
Epithelial Barriers in Homeostasis and Disease
Marchiando, A. M., Graham, W. V., & Turner, J. R. (2010) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev.pathol.4.110807.092135 · Cited by 612 · see citing works
Luissint, A., Parkos, C. A., & Nusrat, A. (2016) · Gastroenterology · doi:10.1053/j.gastro.2016.07.008 · Cited by 561 · see citing works
Interactions Between the Host Innate Immune System and Microbes in Inflammatory Bowel Disease
Abraham, C., & Medzhitov, R. M. (2011) · Gastroenterology · doi:10.1053/j.gastro.2011.02.012 · Cited by 537 · see citing works
Landy, J., Ronde, E., English, N., Clark, S. K., Hart, A. L., Knight, S. C., Ciclitira, P. J., & Al-Hassi, H. O. (2016) · World Journal of Gastroenterology · doi:10.3748/wjg.v22.i11.3117 · Cited by 507 · see citing works
Cell–Cell Junctions Organize Structural and Signaling NetworksPreprint
García, M. Á., Nelson, W. J., & Chavez, N. (2017) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a029181 · Cited by 506 · see citing works
Sturgeon, C., & Fasano, A. (2016) · Tissue Barriers · doi:10.1080/21688370.2016.1251384 · Cited by 497 · see citing works
Fasano, A. (2020) · F1000Research · doi:10.12688/f1000research.20510.1 · Cited by 496 · see citing works
Itallie, C. M. V., Fanning, A. S., Bridges, A. S., & Anderson, J. M. (2009) · Molecular Biology of the Cell · doi:10.1091/mbc.e09-04-0320 · Cited by 479 · see citing works
Pastorelli, L., Salvo, C. D., Mercado, J. R., Vecchi, M. L., & Pizarro, T. T. (2013) · Frontiers in Immunology · doi:10.3389/fimmu.2013.00280 · Cited by 434 · see citing works
Multiple facets of intestinal permeability and epithelial handling of dietary antigens
Ménard, S., Cerf–Bensussan, N., & Heyman, M. (2010) · Mucosal Immunology · doi:10.1038/mi.2010.5 · Cited by 410 · see citing works
Inflammatory and Microbiota-Related Regulation of the Intestinal Epithelial Barrier
Barbara, G., Barbaro, M. R., Fuschi, D., Palombo, M., Falangone, F., Cremon, C., Marasco, G., & Stanghellini, V. (2021) · Frontiers in Nutrition · doi:10.3389/fnut.2021.718356 · Cited by 420 · see citing works
Innate immune mechanisms of colitis and colitis-associated colorectal cancer
Saleh, M., & Trinchieri, G. (2010) · Nature reviews. Immunology · doi:10.1038/nri2891 · Cited by 402 · see citing works
Yu, L. C. (2018) · Journal of Biomedical Science · doi:10.1186/s12929-018-0483-8 · Cited by 404 · see citing works
Su, L., Nalle, S. C., Shen, L., Turner, E. S., Singh, G., Breskin, L. A., Khramtsova, E. A., Khramtsova, G. F., Tsai, P., Fu, Y., et al. (2013) · Gastroenterology · doi:10.1053/j.gastro.2013.04.011 · Cited by 393 · see citing works
Camilleri, M., Lasch, K. L., & Zhou, W. (2012) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00155.2012 · Cited by 397 · see citing works
Peng, Y., Yan, Y., Wan, P., Chen, D., Ding, Y., Ran, L., Mi, J., Lu, L., Zhang, Z., Li, X., et al. (2019) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2019.04.005 · Cited by 392 · see citing works
Kießlich, R., Duckworth, C. A., Moussata, D., Gloeckner, A., Lim, L. G., Goetz, M., Pritchard, D. M., Galle, P. R., Neurath, M. F., & Watson, A. J. M. (2011) · Gut · doi:10.1136/gutjnl-2011-300695 · Cited by 394 · see citing works
Intestinal Permeability Defects: Is It Time to Treat?
Odenwald, M. A., & Turner, J. R. (2013) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2013.07.001 · Cited by 366 · see citing works
Self-citationCytoskeletal Regulation of Epithelial Barrier Function During Inflammation
Ivanov, A. I., Parkos, C. A., & Nusrat, A. (2010) · American Journal Of Pathology · doi:10.2353/ajpath.2010.100168 · Cited by 366 · see citing works
Implication of Intestinal Barrier Dysfunction in Gut Dysbiosis and Diseases
Stolfi, C., Maresca, C., Monteleone, G., & Laudisi, F. (2022) · Biomedicines · doi:10.3390/biomedicines10020289 · Cited by 353 · see citing works
Steck, N., Hoffmann, M., Sava, I. G., Kim, S. C., Hahne, H., Tonkonogy, S. L., Mair, K., Krueger, D., Pruteanu, M., Shanahan, F., et al. (2011) · Gastroenterology · doi:10.1053/j.gastro.2011.05.035 · Cited by 343 · see citing works
Raleigh, D. R., Marchiando, A. M., Zhang, Y., Shen, L., Sasaki, H., Wang, Y., Long, M., & Turner, J. R. (2010) · Molecular Biology of the Cell · doi:10.1091/mbc.e09-08-0734 · Cited by 326 · see citing works
Myosin light chain kinase: pulling the strings of epithelial tight junction function
Cunningham, K. E., & Turner, J. R. (2012) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2012.06526.x · Cited by 345 · see citing works
The tight junction in inflammatory disease: communication breakdown
Edelblum, K. L., & Turner, J. R. (2009) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2009.06.022 · Cited by 313 · see citing works
Chen, P., Stärkel, P., Turner, J. R., Ho, S. B., & Schnabl, B. (2015) · Hepatology · doi:10.1002/hep.27489 · Cited by 312 · see citing works
Self-citationWeber, C. R., Raleigh, D. R., Su, L., Shen, L., Sullivan, E. A., Wang, Y., & Turner, J. R. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.064808 · Cited by 296 · see citing works
The digestive neuronal–glial–epithelial unit: a new actor in gut health and disease
Neunlist, M., Landeghem, L. V., Mahé, M. M., Derkinderen, P., Varannes, S. B. D., & Rolli‐Derkinderen, M. (2012) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2012.221 · Cited by 277 · see citing works
Microbial sensing by goblet cells controls immune surveillance of luminal antigens in the colon
Knoop, K. A., McDonald, K. G., McCrate, S., Mcdole, J. R., & Newberry, R. D. (2014) · Mucosal Immunology · doi:10.1038/mi.2014.58 · Cited by 276 · see citing works
The mucosal barrier at a glance
France, M. M., & Turner, J. R. (2017) · Journal of Cell Science · doi:10.1242/jcs.193482 · Cited by 268 · see citing works
Yu, D., Marchiando, A. M., Weber, C. R., Raleigh, D. R., Wang, Y., Shen, L., & Turner, J. R. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0908869107 · Cited by 256 · see citing works
Gut permeability and mucosal inflammation: bad, good or context dependent
Ahmad, R., Sorrell, M. F., Batra, S. K., Dhawan, P., & Singh, A. B. (2017) · Mucosal Immunology · doi:10.1038/mi.2016.128 · Cited by 243 · see citing works
Inflammation and Disruption of the Mucosal Architecture in Claudin-7–Deficient Mice
Ding, L., Lü, Z., Foreman, O., Tatum, R., Lu, Q., Renegar, R. H., Cao, J. P., & Chen, Y. (2011) · Gastroenterology · doi:10.1053/j.gastro.2011.10.025 · Cited by 219 · see citing works
Tight junctions on the move: molecular mechanisms for epithelial barrier regulation
Shen, L. (2012) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2012.06613.x · Cited by 213 · see citing works
Vitamin D and intestinal homeostasis: Barrier, microbiota, and immune modulation
Fakhoury, H. M. A., Kvietys, P. R., Al-Kattan, W., Anouti, F. A., Elahi, M. A., Karras, S. Ν., & Grant, W. B. (2020) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2020.105663 · Cited by 212 · see citing works
Role of epithelial cells in the pathogenesis and treatment of inflammatory bowel disease
Okamoto, R., & Watanabe, M. (2015) · Journal of Gastroenterology · doi:10.1007/s00535-015-1098-4 · Cited by 203 · see citing works
Gut permeability and food allergies
Perrier, C., & Corthésy, B. (2010) · Clinical & Experimental Allergy · doi:10.1111/j.1365-2222.2010.03639.x · Cited by 203 · see citing works
Role of ion channels in gastrointestinal cancer
Anderson, K. J., Cormier, R. T., & Scott, P. M. (2019) · World Journal of Gastroenterology · doi:10.3748/wjg.v25.i38.5732 · Cited by 204 · see citing works
High-Throughput Screen Identifies Host and Microbiota Regulators of Intestinal Barrier Function
Grosheva, I., Zheng, D., Levy, M., Polansky, O., Lichtenstein, A., Golani, O., Dori-Bachash, M., Moresi, C., Shapiro, H., Mare-Roumani, S. D., et al. (2020) · Gastroenterology · doi:10.1053/j.gastro.2020.07.003 · Cited by 200 · see citing works
Rodríguez‐Nogales, A., Algieri, F., Garrido‐Mesa, J., Vezza, T., Utrilla, M. P., Chueca, N., García, F., Olivares, M. M., Rodríguez‐Cabezas, M. E., & Gálvez, J. (2017) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201700144 · Cited by 191 · see citing works
Tight junctions as targets and effectors of mucosal immune homeostasis
Zuo, L., Kuo, W.-T., & Turner, J. R. (2020) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2020.04.001 · Cited by 191 · see citing works
Amyloid–Polyphenol Hybrid Nanofilaments Mitigate Colitis and Regulate Gut Microbial Dysbiosis
Hu, B., Yu, S., Shi, C., Gu, J., Shao, Y., Chen, Q., Li, Y., & Mezzenga, R. (2020) · ACS Nano · doi:10.1021/acsnano.9b09125 · Cited by 181 · see citing works
Intracellular MLCK1 diversion reverses barrier loss to restore mucosal homeostasis
Graham, W. V., He, W., Marchiando, A. M., Zha, J., Singh, G., Li, H.-S., Biswas, A., Ong, M. L. D. M., Jiang, Z.-H., Choi, W., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0393-7 · Cited by 176 · see citing works
Self-citationTanaka, H., Takechi, M., Kiyonari, H., Shioi, G., Tamura, A., & Tsukita, S. (2015) · Gut · doi:10.1136/gutjnl-2014-308419 · Cited by 175 · see citing works
Shao, Y., Wolf, P. G., Guo, S., Guo, Y., Gaskins, H. R., & Zhang, B. (2017) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2017.01.013 · Cited by 173 · see citing works
Cao, M., Wang, P., Sun, C., He, W., & Wang, F. (2013) · PLoS ONE · doi:10.1371/journal.pone.0061944 · Cited by 168 · see citing works
Intestinal Epithelial Barrier Dysfunction in Disease and Possible Therapeutical Interventions
Catalioto, R.-M., Maggi, C. A., & Giuliani, S. (2011) · Current Medicinal Chemistry · doi:10.2174/092986711794839179 · Cited by 169 · see citing works
Nod2: The intestinal gate keeper
Nabhani, Z. A., Dietrich, G., Hugot, J., & Barreau, F. (2017) · PLoS Pathogens · doi:10.1371/journal.ppat.1006177 · Cited by 168 · see citing works
The NLRP1 inflammasome attenuates colitis and colitis-associated tumorigenesis
Williams, T. M., Leeth, R. A., Rothschild, D. E., Coutermarsh-Ott, S. L., McDaniel, D. K., Simmons, A. E., Heid, B., Cecere, T. E., & Allen, I. C. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1402098 · Cited by 162 · see citing works
IBD Candidate Genes and Intestinal Barrier Regulation
McCole, D. F. (2014) · Inflammatory Bowel Diseases · doi:10.1097/mib.0000000000000090 · Cited by 162 · see citing works
Pyrin Inflammasome Regulates Tight Junction Integrity to Restrict Colitis and Tumorigenesis
Sharma, D., Malik, A., Guy, C. S., Karki, R., Vogel, P., & Kanneganti, T. (2017) · Gastroenterology · doi:10.1053/j.gastro.2017.11.276 · Cited by 162 · see citing works
Yamazaki, D., Funato, Y., Miura, J., Sato, S., Toyosawa, S., Furutani, K., Kurachi, Y., Omori, Y., Furukawa, T., Tsuda, T., et al. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003983 · Cited by 161 · see citing works
Experimental Inflammatory Bowel Disease: Insights into the Host-Microbiota Dialog
Saleh, M., & Elson, C. O. (2011) · Immunity · doi:10.1016/j.immuni.2011.03.008 · Cited by 158 · see citing works
Emerging neuropeptide targets in inflammation: NPY and VIP
Chandrasekharan, B. P., Nezami, B. G., & Srinivasan, S. (2013) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00493.2012 · Cited by 156 · see citing works
Zhu, L., Han, J., Li, L., Wang, Y., Li, Y., & Zhang, S. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01441 · Cited by 151 · see citing works
d'Aldebert, E., Cénac, N., Rousset, P., Martin, L., Rolland, C., Chapman, K., Sèlves, J., Alric, L., Vinel, J., & Vergnolle, N. (2010) · Gastroenterology · doi:10.1053/j.gastro.2010.09.045 · Cited by 154 · see citing works
Tight junctions: from molecules to gastrointestinal diseases
Moonwiriyakit, A., Pathomthongtaweechai, N., Steinhagen, P., Chantawichitwong, P., Satianrapapong, W., & Pongkorpsakol, P. (2022) · Tissue Barriers · doi:10.1080/21688370.2022.2077620 · Cited by 160 · see citing works
Mechanisms and Functional Implications of Intestinal Barrier Defects
Shen, L., Su, L., & Turner, J. R. (2009) · Digestive Diseases · doi:10.1159/000233282 · Cited by 149 · see citing works
Sécher, T., Kassem, S., Benamar, M., Bernard, I., Boury, M., Barreau, F., Oswald, É., & Saoudi, A. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01096 · Cited by 148 · see citing works
Jiang, H., Chen, C., & Gao, J. (2022) · Nutrients · doi:10.3390/nu15010151 · Cited by 149 · see citing works
Tuvia, S., Pelled, D., Marom, K., Salama, P., Levin-Arama, M., Karmeli, I., Idelson, G. H., Landau, I., & Mamluk, R. (2014) · Pharmaceutical Research · doi:10.1007/s11095-014-1303-9 · Cited by 142 · see citing works
Vitamin D, immune regulation, the microbiota, and inflammatory bowel disease
Cantorna, M. T., McDaniel, K. L., Bora, S. A., Chen, J., & James, J. L. (2014) · Experimental Biology and Medicine · doi:10.1177/1535370214523890 · Cited by 140 · see citing works
He, W., Wang, J., Sheng, J.-Y., Zha, J., Graham, W. V., & Turner, J. R. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21030993 · Cited by 140 · see citing works
Leaky gut – concept or clinical entity?
Quigley, E. M. M. (2016) · Current Opinion in Gastroenterology · doi:10.1097/mog.0000000000000243 · Cited by 139 · see citing works
Nalle, S. C., & Turner, J. R. (2015) · Mucosal Immunology · doi:10.1038/mi.2015.40 · Cited by 137 · see citing works
Muñoz, L., Borrero, M., Cantera, M., Conde, E., del Campo, R., Rodríguez‐Serrano, M., Lario, M., Sánchez‐Díaz, A., Pastor, Ó., Díaz, D., et al. (2018) · Hepatology · doi:10.1002/hep.30349 · Cited by 134 · see citing works
Tight junction CLDN2 gene is a direct target of the vitamin D receptor
Zhang, Y., Wu, S., Lu, R., Zhou, D., Zhou, J., Carmeliet, G., Petrof, E. O., Claud, E. C., & Sun, J. (2015) · Scientific Reports · doi:10.1038/srep10642 · Cited by 135 · see citing works
Involvement of Bacteria Other Than Clostridium difficile in Antibiotic-Associated Diarrhoea
Larcombe, S., Hutton, M. L., & Lyras, D. (2016) · Trends in Microbiology · doi:10.1016/j.tim.2016.02.001 · Cited by 135 · see citing works
The Regulation of Intestinal Mucosal Barrier by Myosin Light Chain Kinase/Rho Kinases
Jin, Y., & Blikslager, A. T. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21103550 · Cited by 134 · see citing works
Nighot, P. K., Al–Sadi, R., Rawat, M., Guo, S., Watterson, D. M., & Ma, T. (2015) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00256.2015 · Cited by 132 · see citing works
Patra, A. K., Amasheh, S., & Aschenbach, J. R. (2019) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2018.1486284 · Cited by 130 · see citing works
Crothers, J. W., Chu, N. D., Nguyen, L. T. T., Phillips, M., Collins, C. C., Fortner, K. A., del Río, R., Lavoie, B. A., CALLAS, P. W., Velez, M., et al. (2021) · BMC Gastroenterology · doi:10.1186/s12876-021-01856-9 · Cited by 127 · see citing works
Bacterial proteases in IBD and IBS
Steck, N., Mueller, K., Schemann, M., & Haller, D. (2011) · Gut · doi:10.1136/gutjnl-2011-300775 · Cited by 119 · see citing works
Yang, C., Du, Y., Ren, D., Yang, X., & Zhao, Y. (2021) · Food & Function · doi:10.1039/d1fo01468d · Cited by 123 · see citing works
Moussata, D., Goetz, M., Gloeckner, A., Kerner, M., Campbell, B. J., Hoffman, A. W., Biesterfeld, S., Flourié, B., Saurin, J., Galle, P. R., et al. (2010) · Gut · doi:10.1136/gut.2010.213264 · Cited by 121 · see citing works
Sayoc-Becerra, A., Krishnan, M., Fan, S., Jimenez, J. L., Hernandez, R., Gibson, K., Preciado, R., Butt, G., & McCole, D. F. (2019) · Inflammatory Bowel Diseases · doi:10.1093/ibd/izz266 · Cited by 123 · see citing works
TNF‐α–induced intestinal epithelial cell shedding: implications for intestinal barrier function
Watson, A. J. M., & Hughes, K. R. (2012) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2012.06523.x · Cited by 119 · see citing works
Darsigny, M., Babeu, J., Dupuis, A.-A., Furth, E. E., Seidman, E. G., Levy, E. H., Verdu, E. F., Gendron, F., & Boudreau, F. (2009) · PLoS ONE · doi:10.1371/journal.pone.0007609 · Cited by 120 · see citing works
Mechanisms of Immune Signaling in Colitis-Associated Cancer
Waldner, M. J., & Neurath, M. F. (2014) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2014.11.006 · Cited by 120 · see citing works
Swindle, E. J., Collins, J. E., & Davies, D. E. (2009) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2009.05.037 · Cited by 119 · see citing works
Wu, H. M., Chen, Q.-Y., Wang, W., Chu, S., Liu, X., Liu, Y., Tan, C., Zhu, F., Deng, S., Dong, Y., et al. (2020) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2020.110937 · Cited by 118 · see citing works
Role of Corticotropin-releasing Factor in Gastrointestinal Permeability
Rodiño‐Janeiro, B. K., Alonso, C., Pigrau, M., Lobo, B., Vicario, M., & Santos, J. (2014) · Journal of Neurogastroenterology and Motility · doi:10.5056/jnm14084 · Cited by 119 · see citing works
Wang, W., Xia, T., & Yu, X. (2015) · Inflammation Research · doi:10.1007/s00011-015-0822-0 · Cited by 110 · see citing works
Crohn disease: A current perspective on genetics, autophagy and immunity
Stappenbeck, T. S., Rioux, J. D., Mizoguchi, A., Saitoh, T., Huett, A. S., Darfeuille–Michaud, A., Wileman, T., Mizushima, N., Carding, S. R., Parkes, M., et al. (2011) · Autophagy · doi:10.4161/auto.7.4.13074 · Cited by 109 · see citing works
The Effect of Bacterial Infections, Probiotics and Zonulin on Intestinal Barrier Integrity
Serek, P., & Oleksy-Wawrzyniak, M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222111359 · Cited by 113 · see citing works
Biochemistry of smooth muscle myosin light chain kinase
Hong, F., Haldeman, B. D., Jackson, D. R., Carter, M., Baker, J., & Cremo, C. R. (2011) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2011.04.018 · Cited by 106 · see citing works
Claudin-2-dependent paracellular channels are dynamically gated
Weber, C. R., Liang, G. H., Wang, Y., Das, S., Shen, L., Yu, A. S. L., Nelson, D. J., & Turner, J. R. (2015) · eLife · doi:10.7554/elife.09906 · Cited by 106 · see citing works
Mechanism of Interleukin-1β Induced-Increase in Mouse Intestinal Permeability In Vivo
Al–Sadi, R., Guo, S., Dokładny, K., Smith, M. A., Ye, D., Kaza, A., Watterson, D. M., & Ma, T. Y. (2012) · Journal of Interferon & Cytokine Research · doi:10.1089/jir.2012.0031 · Cited by 105 · see citing works
Algieri, F., Rodríguez‐Nogales, A., Vezza, T., Garrido‐Mesa, J., Garrido‐Mesa, N., Utrilla, M. P., González-Tejero, M. R., Casares-Porcel, M., Mesa, J. M., Contreras, M. D. M., et al. (2016) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2016.05.063 · Cited by 103 · see citing works
- Authors
- Su, L., Shen, L., Clayburgh, D. R., Nalle, S. C., Sullivan, E. A., Meddings, J. B., Abraham, C., & Turner, J. R.
- Affiliations
- University of Chicago (US)
- University of Alberta (CA)
- Yale University (US)
- Corresponding author
- Abraham, Clara
- Turner, Jerrold R.
- ORCID
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2009-02
- Volume
- 136
- Issue
- 2
- Pages
- 551-563
- ISSN
- 0016-5085 (ISSN-L)
- PMC
- PMC2712351
- OpenAlex
- W2131810438
- Cited by
- 455
- References
- 41
- Citations by year
- 2026: 17 · 2025: 17 · 2024: 21 · 2023: 20 · 2022: 29 · 2021: 32 · 2020: 30 · 2019: 19 · 2018: 18 · 2017: 34 · 2016: 29 · 2015: 35 · 2014: 23 · 2013: 23 · 2012: 38
- FWCI
- 12.94
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (T32HL007237)
- National Cancer Institute (P30CA014599)
- National Institute of General Medical Sciences (T32GM007281)
- National Institute of Diabetes and Digestive and Kidney Diseases (P01DK067887, R56DK094954, R01DK077905, R01DK058964, R01DK068271, R01DK061931)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- intestinal epithelial barrier dysfunction, tight junctions, myosin light chain kinase, transgenic mice, experimental colitis, inflammatory bowel disease, mucosal immune activation, interferon-gamma, TNF-α, MHC class I expression, disease susceptibility
- MeSH terms
- Animals, Cell Membrane Permeability, Colitis, Disease Models, Animal, Epithelial Cells, Immunity, Innate, Interferon-gamma, Major Histocompatibility Complex, Mice, Transgenic, Mucous Membrane, Myosin-Light-Chain Kinase, Severity of Illness Index, Tumor Necrosis Factor-alpha, CD4-Positive T-Lymphocytes, Tight Junctions, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review