Toll-Like Receptor 2 Regulates Intestinal Inflammation by Controlling Integrity of the Enteric Nervous System
Open accessAbstract
Background & aims In the intestines, Toll-like receptor 2 (TLR2) mediates immune responses to pathogens and regulates epithelial barrier function; polymorphisms in TLR2 have been associated with inflammatory bowel disease phenotype. We assessed the effects of TLR2 signaling on the enteric nervous system (ENS) in mice. Methods TLR2 distribution and function in the ileal neuromuscular layer of mice were determined by immunofluorescence, cytofluorimetric analysis, immunoprecipitation, and immunoblot analyses. We assessed morphology and function of the ENS in Tlr2(-/-) mice and in mice with wild-type Tlr2 (wild-type mice) depleted of intestinal microbiota, using immunofluorescence, immunoblot, and gastrointestinal motility assays. Levels and signaling of glial cell line-derived neurotrophic factor (GDNF) were determined using quantitative reverse transcriptase polymerase chain reaction, immunohistochemistry, and immunoprecipitation analyses. Colitis was induced by administration of dextran sulfate sodium or 2,4 dinitrobenzensulfonic acid to Tlr2(-/-) mice after termination of GDNF administration. Results TLR2 was expressed in enteric neurons, glia, and smooth muscle cells of the intestinal wall. Tlr2(-/-) mice had alterations in ENS architecture and neurochemical profile, intestinal dysmotility, abnormal mucosal secretion, reduced levels of GDNF in smooth muscle cells, and impaired signaling via Ret-GFRα1. ENS structural and functional anomalies were completely corrected by administration of GDNF to Tlr2(-/-) mice. Wild-type mice depleted of intestinal microbiota had ENS defects and GDNF deficiency, similar to Tlr2(-/-) mice; these defects were partially restored by administration of a TLR2 agonist. Tlr2(-/-) mice developed more severe colitis than wild-type mice after administration of dextran sulfate sodium or 2,4 dinitrobenzensulfonic acid; colitis was not more severe if Tlr2(-/-) mice were given GDNF before dextran sulfate sodium or 2,4 dinitrobenzensulfonic acid. Conclusions In mice, TLR2 signaling regulates intestinal inflammation by controlling ENS structure and neurochemical coding, along with intestinal neuromuscular function. These findings provide information as to how defective TLR2 signaling in the ENS affects inflammatory bowel disease phenotype in humans.
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?
TLR2 is expressed in enteric neurons, glial cells and smooth muscle cells of the intestinal wall.
“In particular, TLR2 is expressed in enteric neurons, glial cells and smooth muscle cells of the intestinal wall.118”
From The role of gut dysbiosis in Parkinson’s disease: mechanistic insights and therapeutic options (2021) · cites this paper as [118]
TLR2 gene-deficient mice had significantly reduced enteric neurons and glial cells and showed stronger colonic inflammation in response to external stimulation.
“Researchers observed that TLR2 gene-deficient (Tlr2 -/-) mice had significantly reduced enteric neurons and glial cells and showed stronger colonic inflammation in response to external stimulation.118”
From The role of gut dysbiosis in Parkinson’s disease: mechanistic insights and therapeutic options (2021) · cites this paper as [118]
Wild-type mice lacking gut microbiota also have enteric nervous system and GDNF deficiencies, which can be partially repaired by administration of TLR2 agonists.
“Furthermore, similar to Tlr2 -/-mice, the wild-type mice lacking gut microbiota also have enteric nervous system and GDNF deficiencies, which can be partially repaired by administration of TLR2 agonists.118”
From The role of gut dysbiosis in Parkinson’s disease: mechanistic insights and therapeutic options (2021) · cites this paper as [118]
TLR2 signalling can regulate intestinal inflammation by modulating enteric nervous system structure, neurochemical coding and intestinal neuromuscular function.
“This research suggests that TLR2 signalling can regulate intestinal inflammation by modulating enteric nervous system structure, neurochemical coding and intestinal neuromuscular function.”
From The role of gut dysbiosis in Parkinson’s disease: mechanistic insights and therapeutic options (2021) · cites this paper as [118]
The microbiome-gut-brain axis is critical in the direct interaction between the gut microbiota and enteric neurons, the production of many chemicals required for brain function, and the regulation of the hypothalamic-pituitary-adrenal axis.
“The GBA is critical in the direct interaction between the gut microbiota and enteric neurons (Barajon et al., 2009; Brun et al., 2013), the production of many chemicals that are required for brain function, and the regulation of the hypothalamic–pituitary–adrenal (HPA) axis (Sudo, 2012).”
From The modulatory effects of gut microbes and metabolites on blood-brain barrier integrity and brain function in sepsis-associated encephalopathy (2023) · cites this paper as Brun et al., 2013
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
Akira, S., & Takeda, K. (2004) · Nature reviews. Immunology · doi:10.1038/nri1391 · Cited by 8,312 · see citing works
The interplay between the intestinal microbiota and the brain
Collins, S. M., Surette, M., & Bercik, P. (2012) · Nature Reviews Microbiology · doi:10.1038/nrmicro2876 · Cited by 1,611 · cited 1× · see citing works
“Most recently, several reports have expanded the role of gut microbiota to directly influencing gut brain axis function, in view of the fact that alterations in microbiota are linked not just to gut inflammation, but also to changes in host behavior.(52) Because stimuli delivered through TLR2 can directly affect immun…”
BackgroundGut microbial products regulate murine gastrointestinal motility via Toll-like receptor 4 signaling
Anitha, M., Vijay–Kumar, M., Sitaraman, S. V., Gewirtz, A. T., & Srinivasan, S. (2012) · Gastroenterology · doi:10.1053/j.gastro.2012.06.034 · Cited by 397 · see citing works
Enteric neuroplasticity evoked by inflammation
Vasina, V., Barbara, G., Talamonti, L., Stanghellini, V., Corinaldesi, R., Tonini, M., De Ponti, F., & De Giorgio, R. (2006) · Autonomic Neuroscience · doi:10.1016/j.autneu.2006.02.025 · Cited by 221 · see citing works
Deschênes-Furry, J., Mousavi, K., Bolognani, F., Neve, R. L., Parks, R. J., Perrone-Bizzozero, N. I., & Jasmin, B. J. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.4626-06.2007 · Cited by 43 · see citing works
Flagged first, then by citations
Research works printed but not linked: 47
- Kawai T, Akira S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol 2010; 11:373-384.
- Sloane JA, Blitz D, Margolin Z, et al. A clear and present danger: endog- enous ligands of Toll-like receptors. Neuromol Med 2010;12:149-163.
- Turer EE, Tavares RM, Mortier E, et al. Homeostatic MyD88- dependent signals cause lethal inflammation in the absence of A20. J Exp Med 2008;205:451-464.
- Rakoff-Nahoum S, Paglino J, Eslami-Varzaneh F, et al. Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis. Cell 2004;118:229-241.
- Rakoff-Nahoum S, Hao L, Medzhitov R. Role of toll-like receptors in spontaneous commensal-dependent colitis. Immunity 2006; 25:319-329.
- Cario E, Gerken G, Podolsky DK. Toll-like receptor 2 controls mucosal inflammation by regulating epithelial barrier function. Gastroenter- ology 2007;132:1359-1374.
- Pierik M, Joossens S, Van Steen K, et al. Toll-like receptor-1, -2, and -6 polymorphisms influence disease extension in inflammatory bowel diseases. Inflamm Bowel Dis 2006;12:1-8.
- Lomax AE, Fernández E, Sharkey KA. Plasticity of the enteric nervous system during intestinal inflammation. Neurogastroenterol Motil 2005;17:4-15.
- Neunlist M, Van Landeghem L, Bourreille A, et al. Neuro-glial crosstalk in inflammatory bowel disease. J Intern Med 2008; 263:577-583.
- Rolls A, Shechter R, London A, et al. Toll-like receptors modulate adult hippocampal neurogenesis. Nat Cell Biol 2007;9:1081-1088.
- Anderson KV, Jurgens G, Nusslein-Volhard C. Establishment of dorsal-ventral polarity in the Drosophila embryo: genetic studies on the role of the Toll gene product. Cell 1985;42:779-789.
- Creedon DJ, Tansey MG, Baloh RH, et al. Neurturin shares receptors and signal transduction pathways with glial cell line-derived neuro- trophic factor in sympathetic neurons. Proc Natl Acad Sci U S A 1997;94:7018-7023.
- Wang H, Hughes I, Planer W, et al. The timing and location of glial cell line-derived neurotrophic factor expression determine enteric nervous system structure and function. J Neurosci 2010; 30:1523-1538.
- Reikvam DH, Erofeev A, Sandvik A, et al. Depletion of murine in- testinal microbiota: effects on gut mucosa and epithelial gene expression. PLoS One 2011;6:e17996.
- Giron MC, Bin A, Brun P, et al. Cyclic AMP in rat ileum: evidence for the presence of an extracellular cyclic AMP-adenosine pathway. Gastroenterology 2008;134:1116-1126.
- Pekny M, Levéen P, Pekna M, et al. Mice lacking glial fibrillary acidic protein display astrocytes devoid of intermediate filaments but develop and reproduce normally. EMBO J 1995;14:1590-1598.
- Donato R, Sorci G, Riuzzi F, et al. S100B's double life: intracellular regulator and extracellular signal. Biochim Biophys Acta 2009; 1793:1008-1022.
- Di Nardo G, Blandizzi C, Volta U, et al. Review article: molecular, pathological and therapeutic features of human enteric neuropa- thies. Aliment Pharmacol Ther 2008;28:25-42.
- Serio R, Zizzo MG, Mulè F. Nitric oxide induces muscular relaxation via cyclic GMP-dependent and -independent mechanisms in the longitu- dinal muscle of the mouse duodenum. Nitric Oxide 2003;8:48-52.
- Snoek SA, Verstege MI, Boeckxstaens GE, et al. The enteric nervous system as a regulator of intestinal epithelial barrier function in health and disease. Expert Rev Gastroenterol Hepatol 2010;4:637-651.
- Bijlsma PB, Bakker R, Groot JA. The chloride conductance of tight junctions of rat ileum can be increased by cAMP but not by carba- chol. J Membr Biol 1997;157:127-137.
- Worley DS, Pisano JM, Choi ED, et al. Developmental regulation of GDNF response and receptor expression in the enteric nervous system. Development 2000;127:4383-4393.
- Gershon MD. Developmental determinants of the independence and complexity of the enteric nervous system. Trends Neurosci 2010; 33:446-456.
- Zhang DK, He FQ, Li TK, et al. Glial-derived neurotrophic factor regulates intestinal epithelial barrier function and inflammation and is therapeutic for murine colitis. J Pathol 2010;222:213-222.
- Yu L, Wang L, Chen S. Endogenous toll-like receptor ligands and their biological significance. J Cell Mol Med 2010;14:2592-2603.
- Wilhelmsen K, Mesa KR, Lucero J, et al. ERK5 protein promotes, whereas MEK1 protein differentially regulates, the Toll-like receptor 2 protein-dependent activation of human endothelial cells and monocytes. J Biol Chem 2012;287:26478-26494.
- Manetsch M, Seidel P, Heintz U, et al. TLR2 ligand engagement upregulates airway smooth muscle TNFa-induced cytokine produc- tion. Am J Physiol Lung Cell Mol Physiol 2012;302:L838-L845.
- Zhang P, Cox CJ, Alvarez KM, et al. Cutting edge: cardiac myosin activates innate immune responses through TLRs. J Immunol 2009; 183:27-31.
- Okun E, Griffioen KJ, Son TG, et al. TLR2 activation inhibits embryonic neural progenitor cell proliferation. J Neurochem 2010;114:462-474.
- Natale G, Pasquali L, Paparelli A, et al. Parallel manifestations of neuropathologies in the enteric and central nervous systems. Neu- rogastroenterol Motil 2011;23:1056-1065.
- Liem RK, Messing A. Dysfunctions of neuronal and glial intermediate filaments in disease. J Clin Invest 2009;119:1814-1824.
- Anitha M, Gondha C, Sutliff RM, et al. GDNF rescues hyperglycemia- induced diabetic enteric neuropathy through activation of the PI3K/ Akt pathway. J Clin Invest 2006;116:344-356.
- Guo C, Quobatari A, Shangguan Y, et al. Diabetic autonomic neu- ropathy: evidence for apoptosis in situ in the rat. Neurogastroenterol Motil 2004;16:335-345.
- Tischfield MA, Engle EC. Distinct alpha-and beta-tubulin isotypes are required for the positioning, differentiation and survival of neurons: new support for the 'multi-tubulin' hypothesis. Biosci Rep 2010; 30:319-330.
- Cirillo C, Sarnelli G, Esposito G, et al. S100b protein in the gut: the evidence for enteroglial-sustained intestinal inflammation. World J Gastroenterol 2011;17:1261-1266.
- Liu W, Yue W, Wu R. Effects of diabetes on expression of glial fibrillary acidic protein and neurotrophins in rat colon. Auton Neu- rosci 2010;154:79-83.
- Savidge TC, Sofroniew MV, Neunlist M. Starring roles for astroglia in barrier pathologies of gut and brain. Lab Invest 2007;87:731-736.
- Kunze WA, Furness JB. The enteric nervous system and regulation of intestinal motility. Annu Rev Physiol 1999;61:117-142.
- Mawe GM, Strong DS, Sharkey KA. Plasticity of enteric nerve func- tions in the inflamed and postinflamed gut. Neurogastroenterol Motil 2009;21:481-491.
- Bsibsi M, Persoon-Deen C, Verwer RW, et al. Toll-like receptor 3 on adult human astrocytes triggers production of neuroprotective me- diators. Glia 2006;53:688-695.
- Rodrigues DM, Li AY, Nair DG, et al. Glial cell line-derived neuro- trophic factor is a key neurotrophin in the postnatal enteric nervous system. Neurogastroenterol Motil 2011;23:e44-e56.
- Rossi J, Luukko K, Poteryaev D, et al. Retarded growth and deficits in the enteric and parasympathetic nervous system in mice lacking GFR alpha2, a functional neurturin receptor. Neuron 1999; 22:243-252.
- Lakhan SE, Kirchgessner A. Neuroinflammation in inflammatory bowel disease. J Neuroinflammation 2010;7:37.
- Ferrante M, de Hertogh G, Hlavaty T, et al. The value of myenteric plexitis to predict early postoperative Crohn's disease recurrence. Gastroenterology 2006;130:1595-1606.
- Wiedermann CJ, Kiechl S, Dunzendorfer S, et al. Association of endotoxemia with carotid atherosclerosis and cardiovascular dis- ease: prospective results from the Bruneck Study. J Am Coll Cardiol 1999;34:1975-1981.
- Erridge C. Endogenous ligands of TLR2 and TLR4: agonists or as- sistants? J Leukoc Biol 2010;87:989-999.
- Wolowczuk I, Verwaerde C, Viltart O, et al. Feeding our immune system: impact on metabolism. Clin Dev Immunol 2008; 2008:639803.
Cited by
Sorted by citations
Martin, C. R., Osadchiy, V., Kalani, A., & Mayer, E. A. (2018) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2018.04.003 · Cited by 1,284 · see citing works
New evidences on the altered gut microbiota in autism spectrum disorders
Strati, F., Cavalieri, D., Albanese, D., De Felice, C., Donati, C., Hayek, J., Jousson, O., Leoncini, S., Renzi, D., Calabrò, A., et al. (2017) · Microbiome · doi:10.1186/s40168-017-0242-1 · Cited by 1,040 · see citing works
Next-Generation Beneficial Microbes: The Case of Akkermansia muciniphila
Cani, P. D., & de Vos, W. M. (2017) · Frontiers in Microbiology · doi:10.3389/fmicb.2017.01765 · Cited by 1,058 · see citing works
The microbiota-gut-brain axis: from motility to mood
Margolis, K. G., Cryan, J. F., & Mayer, E. A. (2021) · Gastroenterology · doi:10.1053/j.gastro.2020.10.066 · Cited by 999 · see citing works
The role of microbiome in central nervous system disorders
Wang, Y., & Kasper, L. H. (2014) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2013.12.015 · Cited by 803 · see citing works
De Vadder, F., Grasset, E., Mannerås Holm, L., Karsenty, G., Macpherson, A. J., Olofsson, L. E., & Bäckhed, F. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1720017115 · Cited by 566 · see citing works
Dimidi, E., Christodoulides, S., Scott, S. M., & Whelan, K. (2017) · Advances in Nutrition · doi:10.3945/an.116.014407 · Cited by 468 · see citing works
Dysbiosis of gut microbiota and microbial metabolites in Parkinson's disease
Sun, M.-F., & Shen, Y.-Q. (2018) · Ageing Research Reviews · doi:10.1016/j.arr.2018.04.004 · Cited by 445 · see citing works
Microbiota controls the homeostasis of glial cells in the gut lamina propria
Kabouridis, P. S., Lasrado, R., McCallum, S., Chng, S. H., Snippert, H. J., Clevers, H., Pettersson, S., & Pachnis, V. (2015) · Neuron · doi:10.1016/j.neuron.2014.12.037 · Cited by 358 · see citing works
Microbiome-Gut-Brain Axis and Toll-Like Receptors in Parkinson’s Disease
Caputi, V., & Giron, M. C. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19061689 · Cited by 338 · see citing works
Self-citationHeiss, C. N., & Olofsson, L. E. (2019) · Journal of Neuroendocrinology · doi:10.1111/jne.12684 · Cited by 304 · see citing works
Modulation of Gut Microbiota–Brain Axis by Probiotics, Prebiotics, and Diet
Liu, X., Cao, S., & Zhang, X. (2015) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.5b02404 · Cited by 304 · see citing works
Interplay between the gut-brain axis, obesity and cognitive function
Agustí, A., García-Pardo, M. P., López-Almela, I., Campillo, I., Maes, M., Romaní-Pérez, M., & Sanz, Y. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00155 · Cited by 294 · see citing works
An integrative view of microbiome-host interactions in inflammatory bowel diseases
Wlodarska, M., Kostic, A. D., & Xavier, R. J. (2015) · Cell Host & Microbe · doi:10.1016/j.chom.2015.04.008 · Cited by 287 · see citing works
The role of gut dysbiosis in Parkinson’s disease: mechanistic insights and therapeutic options
Wang, Q., Luo, Y., Ray Chaudhuri, K., Reynolds, R., Tan, E.-K., & Pettersson, S. (2021) · Brain · doi:10.1093/brain/awab156 · Cited by 281 · see citing works
Dzamko, N., Gysbers, A., Perera, G., Bahar, A., Shankar, A., Gao, J., Fu, Y., & Halliday, G. M. (2017) · Acta Neuropathologica · doi:10.1007/s00401-016-1648-8 · Cited by 273 · see citing works
Pellegrini, C., Antonioli, L., Colucci, R., Blandizzi, C., & Fornai, M. (2018) · Acta Neuropathologica · doi:10.1007/s00401-018-1856-5 · Cited by 270 · see citing works
Bosi, A., Banfi, D., Bistoletti, M., Giaroni, C., & Baj, A. (2020) · International Journal of Tryptophan Research · doi:10.1177/1178646920928984 · Cited by 221 · see citing works
Microbe-host interactions: influence of the gut microbiota on the enteric nervous system
Hyland, N. P., & Cryan, J. F. (2016) · Developmental Biology · doi:10.1016/j.ydbio.2016.06.027 · Cited by 207 · see citing works
Gut Microbiota: The Brain Peacekeeper
Mu, C., Yang, Y., & Zhu, W. (2016) · Frontiers in Microbiology · doi:10.3389/fmicb.2016.00345 · Cited by 188 · see citing works
Pan, R., Wang, L., Xu, X., Chen, Y., Wang, H., Wang, G., Zhao, J., & Chen, W. (2022) · Nutrients · doi:10.3390/nu14183704 · Cited by 149 · see citing works
McVey Neufeld, K. A., Perez‐Burgos, A., Mao, Y. K., Bienenstock, J., & Kunze, W. A. (2015) · Neurogastroenterology & Motility · doi:10.1111/nmo.12534 · Cited by 142 · see citing works
Enteric nervous system: the bridge between the gut microbiota and neurological disorders
Geng, Z.-H., Zhu, Y., Li, Q.-L., Zhao, C., & Zhou, P.-H. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.810483 · Cited by 144 · see citing works
Yarandi, S. S., Kulkarni, S., Saha, M., Sylvia, K. E., Sears, C. L., & Pasricha, P. J. (2020) · Gastroenterology · doi:10.1053/j.gastro.2020.03.050 · Cited by 138 · see citing works
Antibiotic-induced dysbiosis of the microbiota impairs gut neuromuscular function in juvenile mice
Caputi, V., Marsilio, I., Filpa, V., Cerantola, S., Orso, G., Bistoletti, M., Paccagnella, N., De Martin, S., Montopoli, M., Dall'Acqua, S., et al. (2017) · British Journal of Pharmacology · doi:10.1111/bph.13965 · Cited by 124 · see citing works
Self-citationKUWAHARA, A., MATSUDA, K., KUWAHARA, Y., ASANO, S., INUI, T., & MARUNAKA, Y. (2020) · Biomedical Research · doi:10.2220/biomedres.41.199 · Cited by 112 · see citing works
TLR2 and TLR4 in Parkinson’s disease pathogenesis: The environment takes a toll on the gut
Gorecki, A. M., Anyaegbu, C. C., & Anderton, R. S. (2021) · Translational Neurodegeneration · doi:10.1186/s40035-021-00271-0 · Cited by 103 · see citing works
Brun, P., Gobbo, S., Caputi, V., Spagnol, L., Schirato, G., Pasqualin, M., Levorato, E., Palù, G., Giron, M. C., & Castagliuolo, I. (2015) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2015.03.018 · Cited by 92 · see citing works
Self-citationCrosstalk between the immune receptors and gut microbiota
Mu, C., Yang, Y., & Zhu, W. (2015) · Current Protein & Peptide Science · doi:10.2174/1389203716666150630134356 · Cited by 66 · see citing works
Gut Microbiome and Modulation of <scp>CNS</scp> Function
Osadchiy, V., Martin, C. R., & Mayer, E. A. (2019) · Comprehensive Physiology · doi:10.1002/cphy.c180031 · Cited by 53 · see citing works
Li, Z., Zhang, F., Sun, M., Liu, J., Zhao, L., Liu, S., Li, S., & Wang, B. (2023) · PeerJ · doi:10.7717/peerj.15122 · Cited by 43 · see citing works
“The GBA is critical in the direct interaction between the gut microbiota and enteric neurons ( Barajon et al., 2009 ; Brun et al., 2013 ), the production of many chemicals that are required for brain function, and the regulation of the hypothalamic–pituitary–adrenal (HPA) axis ( Sudo, 2012 ).”
Tao, W., Yu, Y., Tan, D., Huang, X., Huang, J., Lin, C., & Yu, R. (2025) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2025.1603442 · Cited by 9 · see citing works
- Authors
- Brun, P., Giron, M. C., Qesari, M., Porzionato, A., Caputi, V., Zoppellaro, C., Banzato, S., Grillo, A. R., Spagnol, L., De Caro, R., Pizzuti, D., Barbieri, V., Rosato, A., Sturniolo, G. C., Martines, D., Zaninotto, G., Palù, G., & Castagliuolo, I.
- Affiliations
- University of Padua (IT)
- Corresponding author
- Giron, Maria Cecilia
- ORCID
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2013-12
- Volume
- 145
- Issue
- 6
- Pages
- 1323-1333
- ISSN
- 0016-5085 (ISSN-L)
- OpenAlex
- W2120027682
- Cited by
- 300
- References
- 5
- Citations by year
- 2026: 15 · 2025: 20 · 2024: 29 · 2023: 21 · 2022: 29 · 2021: 36 · 2020: 27 · 2019: 21 · 2018: 27 · 2017: 17 · 2016: 26 · 2015: 20 · 2014: 9 · 2013: 3
- FWCI
- 16.48
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- Padua Research Archive (University of Padova) (submittedVersion)
- INFM-OAR (INFN Catania) (submittedVersion, other-oa)
- Funders
- European Society of Clinical Microbiology and Infectious Diseases
- Ministero dell’Istruzione, dell’Università e della Ricerca (2007EN8F7T_002, 2009HLNNRL_002)
- Università degli Studi di Padova (CPDA095223)
- Fondazione Cassa di Risparmio di Padova e Rovigo
- Topics
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- TLR2, enteric nervous system, intestinal inflammation, inflammatory bowel disease, glial cell line-derived neurotrophic factor, intestinal dysmotility, gut microbiota, colitis, enteric neurons, smooth muscle cells, enteric glial cells, mucosal secretions, TLR2 knockout mice, dextran sulfate
- MeSH terms
- Animals, Benzenesulfonates, Colitis, Disease Models, Animal, Inflammation, Male, Neuroglia, Neurons, Signal Transduction, Dextran Sulfate, Enteric Nervous System, Mice, Knockout, Glial Cell Line-Derived Neurotrophic Factor, Toll-Like Receptor 2, 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
