Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-6bf8c574d5-5ws7s Total loading time: 0 Render date: 2025-03-06T15:36:40.210Z Has data issue: false hasContentIssue false

11 - Dendritic cells in the gut and their possible role in disease

from IV - Dendritic cells and immune evasion of bacteria in vivo

Published online by Cambridge University Press:  12 August 2009

By
Christoph Becker
Edited by
Maria Rescigno
Maria Rescigno
Affiliation:
European Institute of Oncology, Milan
Get access

Summary

The gut represents the largest lymphoid tissue of the whole body. The delicate task of the intestinal immune system is the discrimination of harmless food antigens and the commensal bacterial flora from harmful pathogens. Under normal physiologic conditions, immune tolerance is induced to non-pathogenic stimuli while effective immune responses are generated toward dangerous pathogens. Thus “decision making” is an important feature of the intestinal immune system. If inappropriate responses are generated, serious inflammation of the small and large intestine may develop. Crohn's disease (CD) and ulcerative colitis are the two prototypes of such inflammatory bowel disease that are believed to develop as a consequence of a disregulated immune response toward harmless antigens. Despite our limited knowledge on the mechanisms of such “decision making” in the gut, recent evidence suggest an important role of intestinal dendritic cells. Dendritic cells (DCs) can be found in large numbers throughout the gastrointestinal tract where they usually build a tight network underlying the epithelium. This chapter will discuss their contribution to the induction of tolerance and immunity in the intestinal immune system as well as a possible role of these DCs in localized immune responses predisposing the terminal ileum for the development of inflammatory bowel disease (IBD).

DENDRITIC CELLS IN THE INTESTINAL IMMUNE SYSTEM: AN OVERVIEW

The intestinal immune system can be functionally separated into an inductive site and an effector site. The prototypic inductive site in the small intestine is the Peyer's patch, a localized lymphoid structure placed within the bowel wall.

Type
Chapter
Information
Dendritic Cell Interactions with Bacteria , pp. 223 - 242
Publisher: Cambridge University Press
Print publication year: 2007

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Mowat, A. M. (2003). Anatomical basis of tolerance and immunity to intestinal antigens. Nat. Rev. Immunol. 3, 331–41CrossRefGoogle ScholarPubMed
Bilsborough, J. and Viney, J. L. (2004). Gastrointestinal dendritic cells play a role in immunity, tolerance, and disease. Gastroenterology 127, 300–9CrossRefGoogle ScholarPubMed
Iwasaki, A. and Kelsall, B. L. (2000). Localization of distinct Peyer's patch dendritic cell subsets and their recruitment by chemokines macrophage inflammatory protein (Mip)-3alpha, Mip-3beta, and secondary lymphoid organ chemokine. J. Exp. Med. 191, 1381–94CrossRefGoogle ScholarPubMed
Kelsall, B. L. and Strober, W. (1996). Distinct populations of dendritic cells are present in the subepithelial dome and T cell regions of the murine Peyer's patch. J. Exp. Med. 183, 237–47CrossRefGoogle Scholar
Iwasaki, A., and Kelsall, B. L. (2001). Unique functions of Cd11b+, Cd8 alpha+, and double-negative Peyer's patch dendritic cells. J. Immunol. 166, 4884–90CrossRefGoogle ScholarPubMed
Macpherson, A. J and Uhr, T. (2004). Induction of protective Iga by intestinal dendritic cells carrying commensal bacteria. Science 303, 1662–5CrossRefGoogle ScholarPubMed
Bilsborough, J., George, T. C., Norment, A., and Viney, J. L. (2003). Mucosal Cd8alpha+ Dc, with a plasmacytoid phenotype, induce differentiation and support function of T cells with regulatory properties. Immunology 108, 481–92CrossRefGoogle ScholarPubMed
Rimoldi, M., Chieppa, M., Salucci, V., Avogadri, F., Sonzogni, A., Sampietro, G. M., Nespoli, A., Viale, G., Allavena, P., and Rescigno, M. (2005). Intestinal immune homeostasis is regulated by the crosstalk between epithelial cells and dendritic cells. Nat. Immunol. 6, 507–14CrossRefGoogle ScholarPubMed
Akbari, O., DeKruyff, R. H., and Umetsu, D. T. (2001). Pulmonary dendritic cells producing Il-10 mediate tolerance induced by respiratory exposure to antigen. Nat. Immunol. 2, 725–31CrossRefGoogle ScholarPubMed
Alpan, O., Rudomen, G., and Matzinger, P. (2001). The role of dendritic cells, B cells, and M cells in gut-oriented immune responses. J. Immunol. 166, 4843–52CrossRefGoogle Scholar
Sato, A., Hashiguchi, M., Toda, E., Iwasaki, A., Hachimura, S., and Kaminogawa, S. (2003). Cd11b+ Peyer's patch dendritic cells secrete Il-6 and induce Iga secretion from naive B cells. J. Immunol. 171, 3684–90CrossRefGoogle ScholarPubMed
Tsuji, N. M., Mizumachi, K., and Kurisaki, J. (2003). Antigen-specific, Cd4+Cd25+ regulatory T cell clones induced in Peyer's patches. Int. Immunol. 15, 525–34CrossRefGoogle ScholarPubMed
Hauet-Broere, F., Unger, W. W., Garssen, J., Hoijer, M. A., Kraal, G., and Samsom, J. N. (2003). Functional Cd25− and Cd25+ mucosal regulatory T cells are induced in gut-draining lymphoid tissue within 48 h after oral antigen application. Eur. J. Immunol. 33, 2801–10CrossRefGoogle ScholarPubMed
Chen, W., Jin, W., Hardegen, N., Lei, K. J., Li, L., Marinos, N., McGrady, G., and Wahl, S. M. (2003). 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. 198, 1875–86CrossRefGoogle ScholarPubMed
Fantini, M. C., Becker, C., Monteleone, G., Pallone, F., Galle, P. R, and Neurath, M. F. (2004). Cutting edge: Tgf-beta induces a regulatory phenotype in Cd4+Cd25− T cells through Foxp3 induction and down-regulation of Smad7. J. Immunol. 172, 5149–53CrossRefGoogle ScholarPubMed
Gonnella, P. A., Chen, Y., Inobe, J., Komagata, Y., Quartulli, M., and Weiner, H. L. (1998). In situ immune response in gut-associated lymphoid tissue (Galt) following oral antigen in Tcr-transgenic mice. J. Immunol. 160, 4708–18Google ScholarPubMed
Jang, M. H., Kweon, M. N., Iwatani, K., Yamamoto, M., Terahara, K., Sasakawa, C., Suzuki, T., Nochi, T., Yokota, Y., Rennert, P. D., Hiroi, T., Tamagawa, H., Iijima, H., Kunisawa, J., Yuki, Y., and Kiyono, H. (2004). Intestinal villous M cells: an antigen entry site in the mucosal epithelium. Proc. Natl Acad. Sci. U S A 101, 6110–15CrossRefGoogle ScholarPubMed
Rescigno, M., Urbano, M., Valzasina, B., Francolini, M., Rotta, G., Bonasio, R., Granucci, F., Kraehenbuhl, J. P., and Ricciardi-Castagnoli, P. (2001). Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria. Nat. Immunol. 2, 361–7CrossRefGoogle ScholarPubMed
Niess, J. H., Brand, S., Gu, X., Landsman, L., Jung, S., McCormick, B. A., Vyas, J. M., Boes, M., Ploegh, H. L., Fox, J. G., Littman, D. R., and Reinecker, H. C. (2005). Cx3cr1-Mediated dendritic cell access to the intestinal lumen and bacterial clearance. Science 307, 254–8CrossRefGoogle ScholarPubMed
Huang, F. P., Platt, N., Wykes, M., Major, J. R., Powell, T. J., Jenkins, C. D., and MacPherson, G. G. (2000). A discrete subpopulation of dendritic cells transports apoptotic intestinal epithelial cells to T cell areas of mesenteric lymph nodes. J. Exp. Med. 191, 435–44CrossRefGoogle Scholar
MacPherson, G. G., Jenkins, C. D., Stein, M. J., and Edwards, C. (1995). Endotoxin-mediated dendritic cell release from the intestine. Characterization of released dendritic cells and Tnf dependence. J. Immunol. 154, 1317–22Google ScholarPubMed
Roake, J. A., Rao, A. S., Morris, P. J., Larsen, C. P., Hankins, D. F., and Austyn, J. M. (1995). Dendritic cell loss from nonlymphoid tissues after systemic administration of lipopolysaccharide, tumor necrosis factor, and interleukin 1. J. Exp. Med. 181, 2237–47CrossRefGoogle ScholarPubMed
Bouma, G. and Strober, W. (2003). The immunological and genetic basis of inflammatory bowel disease. Nat. Rev. Immunol. 3, 521–33CrossRefGoogle ScholarPubMed
Guarner, F. and Malagelada, J. R. (2003). Gut flora in health and disease. Lancet 361, 512–19CrossRefGoogle ScholarPubMed
Shanahan, F. (2002). Crohn's disease. Lancet 359, 62–9CrossRefGoogle ScholarPubMed
Swidsinski, A., Ladhoff, A., Pernthaler, A., Swidsinski, S., Loening-Baucke, V., Ortner, M., Weber, J., Hoffmann, U., Schreiber, S., Dietel, M., and Lochs, H. (2002). Mucosal flora in inflammatory bowel disease. Gastroenterology 122, 44–54CrossRefGoogle ScholarPubMed
Linskens, R. K., Huijsdens, X. W., Savelkoul, P. H., Vandenbroucke-Grauls, C. M., and Meuwissen, S. G. (2001). The bacterial flora in inflammatory bowel disease: current insights in pathogenesis and the influence of antibiotics and probiotics. Scand. J. Gastroenterol. Suppl.29–40CrossRefGoogle ScholarPubMed
Ogura, Y., Bonen, D. K., Inohara, N., Nicolae, D. L., Chen, F. F., Ramos, R., Britton, H., Moran, T., Karaliuskas, R., Duerr, R. H., Achkar, J. P., Brant, S. R., Bayless, T. M., Kirschner, B. S., Hanauer, S. B., Nunez, G., and Cho, J. H. (2001). A frame shift mutation in Nod2 associated with susceptibility to Crohn's disease. Nature 411, 603–6CrossRefGoogle ScholarPubMed
Inohara, N., Ogura, Y., Fontalba, A., Gutierrez, O., Pons, F., Crespo, J., Fukase, K., Inamura, S., Kusumoto, S., Hashimoto, M., Foster, S. J., Moran, A. P., Fernandez-Luna, J. L., and Nunez, G. (2003). Host recognition of bacterial muramyl dipeptide mediated through Nod2. Implications for Crohn's disease. J. Biol. Chem. 278, 5509–12CrossRefGoogle ScholarPubMed
Watanabe, T., Kitani, A., Murray, P. J., and Strober, W. (2004). Nod2 is a negative regulator of Toll-like receptor 2-mediated T helper type 1 responses. Nat. Immunol. 5, 800–8CrossRefGoogle ScholarPubMed
Leach, M. W., Bean, A. G., Mauze, S., Coffman, R. L., and Powrie, F. (1996). Inflammatory bowel disease in C.B-17 Scid mice reconstituted with the Cd45rbhigh subset of Cd4+ T cells. Am. J. Pathol. 148, 1503–15Google ScholarPubMed
Powrie, F., Leach, M. W., Mauze, S., Caddle, L. B., and Coffman, R. L. (1993). Phenotypically distinct subsets of Cd4+ T cells induce or protect from chronic intestinal inflammation in C.B-17 Scid mice. Int. Immunol. 5, 1461–71CrossRefGoogle ScholarPubMed
Leithauser, F., Trobonjaca, Z., Moller, P., and Reimann, J. (2001). Clustering of colonic lamina propria Cd4(+) T cells to subepithelial dendritic cell aggregates precedes the development of colitis in a murine adoptive transfer model. Lab. Invest. 81, 1339–49CrossRefGoogle Scholar
Malmstrom, V., Shipton, D., Singh, B., Al-Shamkhani, A., Puklavec, M. J., Barclay, A. N., and Powrie, F. (2001). Cd134l expression on dendritic cells in the mesenteric lymph nodes drives colitis in T cell-restored Scid mice. J. Immunol. 166, 6972–81CrossRefGoogle Scholar
Krajina, T., Leithauser, F., Moller, P., Trobonjaca, Z., and Reimann, J. (2003). Colonic lamina propria dendritic cells in mice with Cd4+ T cell-induced colitis. Eur. J. Immunol. 33, 1073–83CrossRefGoogle ScholarPubMed
Fuss, I. J., Neurath, M., Boirivant, M., Klein, J. S., Motte, C., Strong, S. A., Fiocchi, C., and Strober, W. (1996). Disparate Cd4+ lamina propria (Lp) lymphokine secretion profiles in inflammatory bowel disease. Crohn's disease Lp cells manifest increased secretion of Ifn-gamma, whereas ulcerative colitis Lp cells manifest increased secretion of Il-5. J. Immunol. 157, 1261–70Google ScholarPubMed
Stuber, E., Strober, W., and Neurath, M. (1996). Blocking the Cd40l–Cd40 interaction in vivo specifically prevents the priming of T helper 1 cells through the inhibition of interleukin 12 secretion. J. Exp. Med. 183, 693–8CrossRefGoogle ScholarPubMed
Monteleone, G., Biancone, L., Marasco, R., Morrone, G., Marasco, O., Luzza, F., and Pallone, F. (1997). Interleukin 12 is expressed and actively released by Crohn's disease intestinal lamina propria mononuclear cells. Gastroenterology 112, 1169–78CrossRefGoogle ScholarPubMed
Neurath, M. F., Fuss, I., Kelsall, B. L., Stuber, E., and Strober, W. (1995). Antibodies to interleukin 12 abrogate established experimental colitis in mice. J. Exp. Med. 182, 1281–90CrossRefGoogle ScholarPubMed
Simpson, S. J., Shah, S., Comiskey, M., Jong, Y. P., Wang, B., Mizoguchi, E., Bhan, A. K., and Terhorst, C. T. (1998). T cell-mediated pathology in two models of experimental colitis depends predominantly on the interleukin 12/signal transducer and activator of transcription (Stat)-4 pathway, but is not conditional on interferon gamma expression by T cells. J. Exp. Med. 187, 1225–34CrossRefGoogle Scholar
Davidson, N. J., Hudak, S. A., Lesley, R. E., Menon, S., Leach, M. W., and Rennick, D. M. (1998). Il-12, but not Ifn-gamma, plays a major role in sustaining the chronic phase of colitis in Il-10-deficient mice. J. Immunol. 161, 3143–9Google ScholarPubMed
Wirtz, S., Finotto, S., Kanzler, S., Lohse, A. W., Blessing, M., Lehr, H. A., Galle, P. R., and Neurath, M. F. (1999). Cutting edge: chronic intestinal inflammation in Stat-4 transgenic mice: characterization of disease and adoptive transfer by Tnf- plus Ifn-gamma-producing Cd4+ T cells that respond to bacterial antigens. J. Immunol. 162, 1884–8Google ScholarPubMed
Mannon, P. J., Fuss, I. J., Mayer, L., Elson, C. O., Sandborn, W. J., Present, D., Dolin, B., Goodman, N., Groden, C., Hornung, R. L., Quezado, M., Neurath, M. F., Salfeld, J., Veldman, G. M., Schwertschlag, U., Strober, W., and Yang, Z. (2004). Anti-interleukin-12 antibody for active Crohn's disease. N. Engl. J. Med. 351, 2069–79CrossRefGoogle ScholarPubMed
Oppmann, B., Lesley, R., Blom, B., Timans, J. C., Xu, Y., Hunte, B., Vega, F., Yu, N., Wang, J., Singh, K., Zonin, F., Vaisberg, E., Churakova, T., Liu, M., Gorman, D., Wagner, J., Zurawski, S., Liu, Y., Abrams, J. S., Moore, K. W., Rennick, D., Waal-Malefyt, R., Hannum, C., Bazan, J. F., and Kastelein, R. A. (2000). Novel P19 protein engages Il-12p40 to form a cytokine, Il-23, with biological activities similar as well as distinct from Il-12. Immunity 13, 715–25CrossRefGoogle Scholar
Cua, D. J., Sherlock, J., Chen, Y., Murphy, C. A., Joyce, B., Seymour, B., Lucian, L., To, W., Kwan, S., Churakova, T., Zurawski, S., Wiekowski, M., Lira, S. A., Gorman, D., Kastelein, R. A., and Sedgwick, J. D. (2003). Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature 421, 744–8CrossRefGoogle ScholarPubMed
Murphy, C. A., Langrish, C. L., Chen, Y., Blumenschein, W., McClanahan, T., Kastelein, R. A., Sedgwick, J. D., and Cua, D. J. (2003). Divergent pro- and antiinflammatory roles for Il-23 and Il-12 in joint autoimmune inflammation. J. Exp. Med. 198, 1951–7CrossRefGoogle ScholarPubMed
Wiekowski, M. T., Leach, M. W., Evans, E. W., Sullivan, L., Chen, S. C., Vassileva, G., Bazan, J. F., Gorman, D. M., Kastelein, R. A., Narula, S., and Lira, S. A. (2001). Ubiquitous transgenic expression of the Il-23 subunit P19 induces multiorgan inflammation, runting, infertility, and premature death. J. Immunol. 166, 7563–70CrossRefGoogle ScholarPubMed
Stallmach, A., Giese, T., Schmidt, C., Ludwig, B., Mueller-Molaian, I., and Meuer, S. C. (2004). Cytokine/chemokine transcript profiles reflect mucosal inflammation in Crohn's disease. Int. J. Colorectal Dis. 19, 308–15CrossRefGoogle ScholarPubMed
Schmidt, C., Giese, T., Ludwig, B., Mueller-Molaian, I., Marth, T., Zeuzem, S., Meuer, S. C., and Stallmach, A. (2005). Expression of interleukin-12-related cytokine transcripts in inflammatory bowel disease: elevated interleukin-23p19 and interleukin-27p28 in Crohn's disease but not in ulcerative colitis. Inflamm. Bowel Dis. 11, 16–23CrossRefGoogle ScholarPubMed
Fujino, S., Andoh, A., Bamba, S., Ogawa, A., Hata, K., Araki, Y., Bamba, T., and Fujiyama, Y. (2003). Increased expression of interleukin 17 in inflammatory bowel disease. Gut 52, 65–70CrossRefGoogle ScholarPubMed
Nielsen, O. H., Kirman, I., Rudiger, N., Hendel, J., and Vainer, B. (2003). Upregulation of interleukin-12 and -17 in active inflammatory bowel disease. Scand. J. Gastroenterol. 38, 180–5CrossRefGoogle ScholarPubMed
Parham, C., Chirica, M., Timans, J., Vaisberg, E., Travis, M., Cheung, J., Pflanz, S., Zhang, R., Singh, K. P., Vega, F., To, W., Wagner, J., O'Farrell, A. M., McClanahan, T., Zurawski, S., Hannum, C., Gorman, D., Rennick, D. M., Kastelein, R. A., Waal Malefyt, R., and Moore, K. W. (2002). A receptor for the heterodimeric cytokine Il-23 is composed of Il-12rbeta1 and a novel cytokine receptor subunit, Il-23r. J. Immunol. 168, 5699–708CrossRefGoogle Scholar
Eijnden, S. V., Goriely, S., Wit, D., Willems, F., and Goldman, M. (2005). Il-23 up-regulates Il-10 and induces Il-17 synthesis by polyclonally activated naive T cells in human. Eur. J. Immunol. 35, 469–75CrossRefGoogle Scholar
Aggarwal, S., Ghilardi, N., Xie, M. H., Sauvage, F. J., and Gurney, A. L. (2003). Interleukin-23 promotes a distinct Cd4 T cell activation state characterized by the production of interleukin-17. J. Biol. Chem. 278, 1910–14CrossRefGoogle ScholarPubMed
Happel, K. I., Zheng, M., Young, E., Quinton, L. J., Lockhart, E., Ramsay, A. J., Shellito, J. E., Schurr, J. R., Bagby, G. J., Nelson, S., and Kolls, J. K. (2003). Cutting edge: roles of Toll-like receptor 4 and Il-23 in Il-17 expression in response to Klebsiella pneumoniae infection. J. Immunol. 170, 4432–6CrossRefGoogle ScholarPubMed
Langrish, C. L., Chen, Y., Blumenschein, W. M., Mattson, J., Basham, B., Sedgwick, J. D., McClanahan, T., Kastelein, R. A., and Cua, D. J. (2005). Il-23 drives a pathogenic T cell population that induces autoimmune inflammation. J. Exp. Med. 201, 233–40CrossRefGoogle ScholarPubMed
Kolls, J. K. and Linden, A. (2004). Interleukin-17 family members and inflammation. Immunity 21, 467–76CrossRefGoogle ScholarPubMed
Fossiez, F., Djossou, O., Chomarat, P., Flores-Romo, L., Ait-Yahia, S., Maat, C., Pin, J. J., Garrone, P., Garcia, E., Saeland, S., Blanchard, D., Gaillard, C., Das Mahapatra, B., Rouvier, E., Golstein, P., Banchereau, J., and Lebecque, S. (1996). T cell interleukin-17 induces stromal cells to produce proinflammatory and hematopoietic cytokines. J. Exp. Med. 183, 2593–603CrossRefGoogle ScholarPubMed
Jovanovic, D. V., Di Battista, J. A., Martel-Pelletier, J., Jolicoeur, F. C., He, Y., Zhang, M., Mineau, F., and Pelletier, J. P. (1998). Il-17 stimulates the production and expression of proinflammatory cytokines, Il-beta and Tnf-alpha, by human macrophages. J. Immunol. 160, 3513–21Google ScholarPubMed
Molet, S., Hamid, Q., Davoine, F., Nutku, E., Taha, R., Page, N., Olivenstein, R., Elias, J., and Chakir, J. (2001). Il-17 is increased in asthmatic airways and induces human bronchial fibroblasts to produce cytokines. J. Allergy Clin. Immunol. 108, 430–8CrossRefGoogle ScholarPubMed
Antonysamy, M. A., Fanslow, W. C., Fu, F., Li, W., Qian, S., Troutt, A. B., and Thomson, A. W. (1999). Evidence for a role of Il-17 in organ allograft rejection: Il-17 promotes the functional differentiation of dendritic cell progenitors. J. Immunol. 162, 577–84Google ScholarPubMed
Wu, C. Y., Kirman, J. R., Rotte, M. J., Davey, D. F., Perfetto, S. P., Rhee, E. G., Freidag, B. L., Hill, B. J., Douek, D. C., and Seder, R. A. (2002). Distinct lineages of T(H)1 cells have differential capacities for memory cell generation in vivo. Nat. Immunol. 3, 852–8CrossRefGoogle Scholar
Powrie, F., Leach, M. W., Mauze, S., Menon, S., Caddle, L. B., and Coffman, R. L. (1994). Inhibition of Th1 responses prevents inflammatory bowel disease in Scid mice reconstituted with Cd45rbhi Cd4+ T cells. Immunity 1, 553–62CrossRefGoogle ScholarPubMed
Ito, H. and Fathman, C. G. (1997). Cd45rbhigh Cd4+ T cells from Ifn-gamma knockout mice do not induce wasting disease. J. Autoimmun. 10, 455–9CrossRefGoogle Scholar
Bregenholt, S., Brimnes, J., Nissen, M. H., and Claesson, M. H. (1999). In vitro activated Cd4+ T cells from interferon-gamma (Ifn-gamma)-deficient mice induce intestinal inflammation in immunodeficient hosts. Clin. Exp. Immunol. 118, 228–34CrossRefGoogle ScholarPubMed
Berg, D. J., Davidson, N., Kuhn, R., Muller, W., Menon, S., Holland, G., Thompson-Snipes, L., Leach, M. W., and Rennick, D. (1996). Enterocolitis and colon cancer in interleukin-10-deficient mice are associated with aberrant cytokine production and Cd4(+) Th1-like responses. J. Clin. Invest. 98, 1010–20CrossRefGoogle ScholarPubMed
Pflanz, S., Timans, J. C., Cheung, J., Rosales, R., Kanzler, H., Gilbert, J., Hibbert, L., Churakova, T., Travis, M., Vaisberg, E., Blumenschein, W. M., Mattson, J. D., Wagner, J. L., To, W., Zurawski, S., McClanahan, T. K., Gorman, D. M., Bazan, J. F., Waal Malefyt, R., Rennick, D., and Kastelein, R. A. (2002). Il-27, a heterodimeric cytokine composed of Ebi3 and P28 protein, induces proliferation of naive Cd4(+) T cells. Immunity 16, 779–90CrossRefGoogle ScholarPubMed
Lucas, S., Ghilardi, N., Li, J., and Sauvage, F. J. (2003). Il-27 regulates Il-12 responsiveness of naive Cd4+ T cells through Stat1-dependent and -independent mechanisms. Proc. Natl Acad. Sci. U S A 100, 15047–52CrossRefGoogle ScholarPubMed
Takeda, A., Hamano, S., Yamanaka, A., Hanada, T., Ishibashi, T., Mak, T. W., Yoshimura, A., and Yoshida, H. (2003). Cutting edge: role of Il-27/Wsx-1 signaling for induction of T-Bet through activation of Stat1 during initial Th1 commitment. J. Immunol. 170, 4886–90CrossRefGoogle ScholarPubMed
Nieuwenhuis, E. E., Neurath, M. F., Corazza, N., Iijima, H., Trgovcich, J., Wirtz, S., Glickman, J., Bailey, D., Yoshida, M., Galle, P. R., Kronenberg, M., Birkenbach, M., and Blumberg, R. S. (2002). Disruption of T helper 2-immune responses in Epstein–Barr virus-induced gene 3-deficient mice. Proc. Natl Acad. Sci. U S A 99, 16951–6CrossRefGoogle Scholar
Wang, J. and Fu, Y. X. (2005). Tumor necrosis factor family members and inflammatory bowel disease. Immunol. Rev. 204, 144–55CrossRefGoogle ScholarPubMed
Atreya, R., Mudter, J., Finotto, S., Mullberg, J., Jostock, T., Wirtz, S., Schutz, M., Bartsch, B., Holtmann, M., Becker, C., Strand, D., Czaja, J., Schlaak, J. F., Lehr, H. A., Autschbach, F., Schurmann, G., Nishimoto, N., Yoshizaki, K., Ito, H., Kishimoto, T., Galle, P. R., Rose-John, S., and Neurath, M. F. (2000). Blockade of interleukin 6 trans signaling suppresses T-cell resistance against apoptosis in chronic intestinal inflammation: evidence in Crohn's disease and experimental colitis in vivo. Nat. Med. 6, 583–8CrossRefGoogle ScholarPubMed
Strober, W., Fuss, I. J., and Blumberg, R. S. (2002). The immunology of mucosal models of inflammation. Annu. Rev. Immunol. 20, 495–549CrossRefGoogle ScholarPubMed
Yamanaka, T., Helgeland, L., Farstad, I. N., Fukushima, H., Midtvedt, T., and Brandtzaeg, P. (2003). Microbial colonization drives lymphocyte accumulation and differentiation in the follicle-associated epithelium of Peyer's patches. J. Immunol. 170, 816–22CrossRefGoogle ScholarPubMed
Onderdonk, A. B., Richardson, J. A., Hammer, R. E., and Taurog, J. D. (1998). Correlation of cecal microflora of Hla-B27 transgenic rats with inflammatory bowel disease. Infect. Immun. 66, 6022–3Google ScholarPubMed
Rath, H. C., Ikeda, J. S., Linde, H. J., Scholmerich, J., Wilson, K. H., and Sartor, R. B. (1999). Varying cecal bacterial loads influences colitis and gastritis in Hla-B27 transgenic rats. Gastroenterology 116, 310–19CrossRefGoogle ScholarPubMed
Mizoguchi, A., Mizoguchi, E., Chiba, C., and Bhan, A. K. (1996). Role of appendix in the development of inflammatory bowel disease in Tcr-alpha mutant mice. J. Exp. Med. 184, 707–15CrossRefGoogle ScholarPubMed
May, E., Lambert, C., Holtmeier, W., Hennemann, A., Zeitz, M., and Duchmann, R. (2002). Regional variation of the alphabeta T cell repertoire in the colon of healthy individuals and patients with Crohn's disease. Hum. Immunol. 63, 467–80CrossRefGoogle ScholarPubMed
Kuckelkorn, U., Ruppert, T., Strehl, B., Jungblut, P. R., Zimny-Arndt, U., Lamer, S., Prinz, I., Drung, I., Kloetzel, P. M., Kaufmann, S. H., and Steinhoff, U. (2002). Link between organ-specific antigen processing by 20s proteasomes and Cd8(+) T cell-mediated autoimmunity. J. Exp. Med. 195, 983–90CrossRefGoogle ScholarPubMed
Becker, C., Wirtz, S., Blessing, M., Pirhonen, J., Strand, D., Bechthold, O., Frick, J., Galle, P. R., Autenrieth, I., and Neurath, M. F. (2003). Constitutive P40 promoter activation and Il-23 production in the terminal ileum mediated by dendritic cells. J. Clin. Invest. 112, 693–706CrossRefGoogle ScholarPubMed

Save book to Kindle

To save this book to your Kindle, first ensure [email protected] is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×