Skip to main content Accesibility Help

The role of enteric glia in gut inflammation

  • Georg von Boyen (a1) and Martin Steinkamp (a2)

A neuro-glia interaction is part of gut inflammation and essential for the integrity of the bowel. A loss of enteric glia cells (EGCs) led to a fatal haemorrhagic jejuno-ileitis and death in a few days. Although a diminished EGC network is postulated in inflammatory bowel disease and enteric glia pathology is described in Chagas' disease the role of EGCs in the onset of these disease complexes is not definitely clear. Several lines of evidence implicate that the secretion of different factors by enteric glia may be the key for modulating gut homeostasis. As mucosal integrity might be important for remission in Crohn's disease and inflammation of the enteric nervous system is part of the pathology in Chagas' disease, the role of EGCs during gut inflammation could be part of the key to understand these diseases.

Corresponding author
Correspondence should be addressed to: Georg von Boyen, Klinik für Innere Medizin I, Universitätsklinikum Ulm, Albert-Einstein Allee 23, 89081 Ulm, Germany phone: +49 731 500 44603 fax: +49 731 500 44610 email:
Hide All
Abdo, H., Derkinderen, P., Gomes, P., Chevalier, J., Aubert, P., Masson, D. et al. (2010) Enteric glial cells protect neurons from oxidative stress in part via reduced gluthatione. FASEB Journal 24, 10821094.
Baert, F., Moortgat, L., Van Assche, G., Caenepeel, P., Vergauwe, P., De Vos, M. et al. (2010) Belgian inflammatory bowel disease research group; North-Holland Gut Club. Mucosal healing predicts sustained clinical remission in patients with early-stage Crohn's disease. Gastroenterology 138, 463468.
Bush, T.G. (2002) Enteric glial cells. An upstream target for induction of necrotizing enterocolitis and Crohn's disease? Bioessays 24, 130140.
Bush, T.G., Savidge, T.C., Freeman, T.C., Cox, H.J., Campbell, E.A., Mucke, L. et al. (1998) Fulminant jejuno-ileitis following ablation of enteric glia in adult transgenic mice. Cell 93, 189201.
Cabarrocas, J., Savidge, T. and Liblau, R. (2003) Role of enteric glial cells in inflammatory bowel disease. Glia 41, 8193.
Colombel, J.F., Sandborn, W.J., Reinisch, W., Mantzaris, G.J., Kornbluth, A., Rachmilewitz, D., et al. ; SONIC Study Group (2010) Infliximab, azathioprine or combination therapy for Crohn's disease. New England Journal of Medicine 362, 13831395.
Cornet, A., Savidge, T.C., Cabarrocas, J., Deng, W.L., Colombel, J.F., Lassmann, H. et al. (2001) Enterocolitis induced by autoimmune targeting of enteric glial cells: a possible mechanism in Crohn's disease? Proceedings of the National Academy of Sciences of the U.S.A. 98, 1330613311.
Daperno, M., D'Haens, G., Van Assche, G., Baert, F., Bulois, P., Maunoury, V. et al. (2004) Development and validation of a new, simplified endoscopic activity score for Crohn's disease: the SES-CD. Gastrointestinal Endoscopy 60, 505512.
da Silveira, A.B., de Oliveira, E.C., Neto, S.G., Luquetti, A.O., Fujiwara, R.T., Oliveira, R.C. et al. (2011) Enteroglial cells act as antigen-presenting cells in chagasic megacolon. Human Pathology 42, 522532.
da Silveira, A.B., Freitas, M.A., de Oliveira, E.C., Neto, S.G., Luquetti, A.O., Furness, J.B. et al. (2009) Glial fibrillary acidic protein and S-100 colocalization in the enteroglial cells in dilated and nondilated portions of colon from chagasic patients. Human Pathology 40, 244251.
da Silveira, A.B., Lemos, E.M., Adad, S.J., Correa-Oliveira, R., Furness, J.B. and D'Avila Reis, D. (2007) Megacolon in Chagas disease: a study of inflammatory cells, enteric nerves, and glial cells. Human Pathology 38, 12561264.
de Souza, W., de Carvalho, T.M. and Barrias, E.S. (2010) Review on Trypanosoma cruzi: host cell interaction. International Journal of Cell Biology 2010, 112
D'Haens, G.R., Noman, M., Baert, F., Vermeire, S. and Van Assche, G. (2002) Endoscopic healing after infliximab treatment for Crohn's disease provides a longer time to relapse. Gastroenterology 122, A776.
Dias, J.C. (1989) The indeterminate form of human chronic Chagas' disease. A clinical epidemiological review. Revista da Sociedade Brasileira de Medicina Tropical 22, 147156.
Ferri, G.L., Probert, L., Cocchia, D., Michetti, F., Marangos, P.J. and Polak, J.M. (1982) Evidence for the presence of S-100 protein in the glial component of the human enteric nervous system. Nature 297, 409410.
Frøslie, K.F., Jahnsen, J., Moum, B.A. and Vatn, M.H.; IBSEN Group (2007) Mucosa healing in inflammatory bowel disease: results from a Norwegian population-based cohort. Gastroenterology 133, 412422.
Gabella, G. (1981) Ultrastructure of the nerve plexuses of the mammalian intestine: the enteric glial cells. Neuroscience 6, 425436.
Geboes, K., Rutgeerts, P., Ectors, N., Mebis, J., Penninckx, F., Vantrappen, G. et al. (1992) Major histocompatibility class II expression on the small intestinal nervous system in Crohn's disease. Gastroenterology 103, 439447.
Gershon, M.D. and Rothman, T.P. (1991) Enteric glia. Glia 4, 195204.
Hollenbach, E., Rühl, A., Zoller, M. and Stremmel, W. (2000) T cell activation by enteric glia: a novel pathway for the amplification of inflammatory responses in the enteric nervous system. Gastroenterology 118, A184.
Irvine, E.J. and Marshall, J.K. (2000) Increased intestinal permeability precedes the onset of Crohn's disease in a subject with familial risk. Gastroenterology 119, 17401744.
Jessen, K.R. and Mirsky, R. (1980) Glial cells in the enteric nervous system contain glial fibrillary acidic protein. Nature 286, 736737.
Koretz, K., Momburg, F., Otto, H.F. and Moller, P. (1984) Sequential induction of MHC antigens on autochtonous cells of ileum affected by Crohn's disease. American Journal of Pathology 129, 493502.
Krammer, H.J. and Kühnel, W. (1993) Topography of the enteric nervous system in Peyer's patches of the porcine small intestine. Cell Tissue Research 272, 267272.
Krammer, H.J., Süss, A., Singer, M.V. and Wedel, T. (2002) Neurogastroenterology – from the basics to the clinics. Romanian Journal of Gastroenterology 11, 313319.
Nascimento, R.D., de Souza Lisboa, A., Fujiwara, R.T., de Freitas, M.A., Adad, S.J., Oliveira, R.C. et al. (2010) Characterization of enteroglial cells and denervation process in chagasic patients with and without megaesophagus. Human Pathology 41, 528534.
Neunlist, M., Aubert, P., Bonnaud, S., Van Landeghem, L., Coron, E., Wedel, T. et al. (2007) Enteric glia inhibit intestinal epithelial cell proliferation partly through a TGF-beta1-dependent pathway. American Journal of Physiology – Gastrointestinal and Liver Physiology 292, G231G241.
Neunlist, M., Van Landeghem, L., Bourreille, A. and Savidge, T. (2008) Neuro-glial crosstalk in inflammatory bowel disease. Journal of Internal Medicine 263, 577583.
Oliveira, E.C., Fujisawa, M.M., Hallal Longo, D.E., Farias, A.S., Contin Moraes, J, Guariento, M.E. et al. (2009) Neuropathy of gastrointestinal Chagas' disease: immune response to myelin antigens. Neuroimmunomodulation 16, 5462.
Radke, R. and Krammer, H.J. (1996) Enteric nervous system similarities and differences in the gastrointestinal tract, gallbladder and pancreas. Neurogastroenterologia 3, 93105.
Reed, S.G. (1998) Immunology of Trypanosoma cruzi infections. Chemical Immunology 70, 124143.
Reinshagen, M., Rohm, H., Steinkamp, M., Lieb, K., Geerling, I., Von Herbay, A. et al. (2000) Protective role of neurotrophins in experimental inflammation of the rat gut. Gastroenterology 119, 368376.
Rühl, A., Franzke, S., Collins, S.M. and Stremmel, W. (2001) Interleukin-6 expression and regulation in rat enteric glia cells. American Journal of Physiology – Gastrointestinal and Liver Physiology 280, G11631171.
Rutgeerts, P., Geboes, K., Vantrappen, G., Beyls, J., Kerremans, R. and Hiele, M. (1990) Predictability of the postoperative course of Crohn's disease. Gastroenterology 99, 956963.
Rutgeerts, P., Geboes, K., Vantrappen, G., Kerremans, R., Coenegrachts, J.L., and Coremans, G. (1984) Natural history of recurrent Crohn's disease at the ileocolonic anastomosis after curative surgery. Gut 25, 665672.
Savidge, T.C., Newman, P., Pothoulakis, C., Ruhl, A., Neunlist, M., Bourreille, A. et al. (2007a) Enteric glia regulate intestinal barrier function and inflammation via release of S-nitrosoglutathione. Gastroenterology 132, 13441358.
Savidge, T.C., Sofroniew, M.V. and Neunlist, M. (2007b) Starring roles for astroglia in barrier pathologies of gut and brain. Laboratory Investigation 87, 731736.
Shanahan, F. (2001) Inflammatory bowel disease: immunodiagnostics, immunotherapeutics, and ecotherapeutics. Gastroenterology 120, 622635.
Sokol, H., Polin, V., Lavergne-Slove, A., Panis, Y., Treton, X., Dray, X. et al. (2009) Plexitis as a predictive factor of early postoperative clinical recurrence in Crohn's disease. Gut 58, 12181225.
Steinkamp, M., Geerling, I., Seufferlein, T., von Boyen, G., Egger, B., Grossmann, J. et al. (2003) Glial-derived neurotrophic factor regulates apoptosis in colonic epithelial cells. Gastroenterology 124, 17481757.
von Boyen, G.B., Degenkolb, N., Hartmann, C., Adler, G. and Steinkamp, M. (2010) The endothelin axis influences enteric glia cell functions. Medical Science Monitor 16, BR161BR167.
von Boyen, G.B., Reinshagen, M., Steinkamp, M., Adler, G. and Kirsch, J. (2002a) Gut inflammation modulated by the enteric nervous system and neurotrophic factors. Scandinavian Journal of Gastroenterology 37, 621625.
von Boyen, G.B., Reinshagen, M., Steinkamp, M., Adler, G. and Kirsch, J. (2002b) Enteric nervous plasticity and development: dependence on neurotrophic factors. Journal of Gastroenterology 37, 583588.
von Boyen, G.B., Schulte, N., Pfluger, C., Spaniol, U., Hartmann, C. and Steinkamp, M. (2011) Distribution of enteric glia and GDNF during gut inflammation. BMC Gastroenterology 11, 3. [Epub ahead of print]
von Boyen, G.B., Steinkamp, M., Geerling, I., Reinshagen, M., Schäfer, K.H., Adler, G. et al. (2006a) Proinflammatory cytokines induce neurotrophic factor expression in enteric glia: a key to the regulation of epithelial apoptosis in Crohn's disease. Inflammatory Bowel Disease 12, 346354.
von Boyen, G.B., Steinkamp, M., Reinshagen, M., Schäfer, K.H., Adler, G. and Kirsch, J. (2004) Proinflammatory cytokines increase glial fibrillary acidic protein expression in enteric glia. Gut 53, 222228.
von Boyen, G.B., Steinkamp, M., Reinshagen, M., Schäfer, K.H., Adler, G. and Kirsch, J. (2006b) Nerve growth factor secretion in cultured enteric glia cells is modulated by proinflammatory cytokines. Journal of Neuroendocrinology 18, 820825.
Walz, W. (2000) Controversy surrounding the existence of discrete functional classes of astrocytes in adult gray matter. Glia 31, 95103.
Walz, W. and Lang, M.K. (1998) Immunocytochemical evidence for a distinct GFAPnegative subpopulation of astrocytes in the adult rat hippocampus. Neuroscience Letters 257, 127130.
Wedel, T., Roblick, U., Gleiss, J., Schiedeck, T., Bruch, H.P., Kühnel, W. et al. (1999) Organization of the enteric nervous system in the human colon demonstrated by wholemount immunohistochemistry with special reference to the submucous plexus. Annals of Anatomy 181, 327337.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Neuron Glia Biology
  • ISSN: 1740-925X
  • EISSN: 1741-0533
  • URL: /core/journals/neuron-glia-biology
Please enter your name
Please enter a valid email address
Who would you like to send this to? *



Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed