Digestive Diseases and Sciences

, Volume 56, Issue 1, pp 79–89 | Cite as

Induction and Activation of Adaptive Immune Populations During Acute and Chronic Phases of a Murine Model of Experimental Colitis

  • Lindsay J. HallEmail author
  • Emilie Faivre
  • Aoife Quinlan
  • Fergus Shanahan
  • Kenneth Nally
  • Silvia Melgar
Original Article



Dextran sodium sulphate (DSS) is commonly used to induce intestinal inflammation in rodents. Despite its continuing importance as a model system for examining IBD pathogenesis, the mucosal and systemic immune responses have not been comprehensively documented.


The purpose of this study was to dissect functional and phenotypic changes in both immune compartments associated with acute and chronic DSS-induced colitis.


C57BL/6 mice were exposed to 3% DSS for 6 days followed by 20 days of water, and organs (spleens, MLN and colons) were harvested during both acute and chronic phases of colitis to examine innate and adaptive cell populations.


As early as 1 day post DSS, significant changes in the percentage, distribution and activation status of all innate cell populations examined were noted. These striking differences continued in systemic and mucosal lymphoid tissues throughout the acute phase (days 5–12). Significantly, during the late acute and chronic phases T and B cells accumulated in the colon. In contrast, in the spleens of chronically inflamed mice T and B cells were significantly decreased whereas neutrophils, macrophages, and IL-6 and IL-17 positive cells were increased.


Our data provides important insights into the mucosal and systemic immune responses induced by DSS administration. Notably, we show that adaptive immune responses are induced during both acute and chronic colitis. This will facilitate a more informed and sophisticated use of this model both for investigating basic mechanisms of intestinal inflammation and for the evaluation of potential new therapeutic agents for IBD.


Dextran sodium sulphate Colitis Innate Adaptive immune responses 



The Alimentary Pharmabiotic Centre is a research centre funded by Science Foundation Ireland (SFI), through the Irish Government’s National Development Plan. The authors and their work were supported by SFI (grant no.s 02/CE/B124 and 07/CE/B1368) and by additional grants from industry including GlaxoSmithKline Ltd.

Conflict of interest statement



  1. 1.
    Korzenik JR, Podolsky DK. Evolving knowledge and therapy of inflammatory bowel disease. Nat Rev Drug Discov. 2006;5:197–209.CrossRefPubMedGoogle Scholar
  2. 2.
    Cho JH. The genetics and immunopathogenesis of inflammatory bowel disease. Nat Rev. 2008;8:458–466.CrossRefGoogle Scholar
  3. 3.
    Xavier RJ, Podolsky DK. Unravelling the pathogenesis of inflammatory bowel disease. Nature. 2007;448:427–434.CrossRefPubMedGoogle Scholar
  4. 4.
    Byrne FR, Viney JL. Mouse models of inflammatory bowel disease. Curr Opin Drug Discov Dev. 2006;9:207–217.Google Scholar
  5. 5.
    Melgar S, Karlsson A, Michaelsson E. Acute colitis induced by dextran sulfate sodium progresses to chronicity in C57BL/6 but not in BALB/c mice: correlation between symptoms and inflammation. Am J Physiol. 2005;288:G1328–G1338.Google Scholar
  6. 6.
    Ni J, Chen SF, Hollander D. Effects of dextran sulphate sodium on intestinal epithelial cells and intestinal lymphocytes. Gut. 1996;39:234–241.CrossRefPubMedGoogle Scholar
  7. 7.
    Kitajima S, Takuma S, Morimoto M. Changes in colonic mucosal permeability in mouse colitis induced with dextran sulfate sodium. Experimental Anim. 1999;48:137–143.CrossRefGoogle Scholar
  8. 8.
    Okayasu I, Hatakeyama S, Yamada M, Ohkusa T, Inagaki Y, Nakaya R. A novel method in the induction of reliable experimental acute and chronic ulcerative colitis in mice. Gastroenterology. 1990;98:694–702.PubMedGoogle Scholar
  9. 9.
    Kuhl AA, Kakirman H, Janotta M, et al. Aggravation of different types of experimental colitis by depletion or adhesion blockade of neutrophils. Gastroenterology. 2007;133:1882–1892.CrossRefPubMedGoogle Scholar
  10. 10.
    Farooq SM, Stillie R, Svensson M, Svanborg C, Strieter RM, Stadnyk AW. Therapeutic effect of blocking CXCR2 on neutrophil recruitment and dextran sodium sulfate-induced colitis. J Pharmacol Exp Ther. 2009;329:123–129.CrossRefPubMedGoogle Scholar
  11. 11.
    Teahon K, Smethurst P, Pearson M, Levi AJ, Bjarnason I. The effect of elemental diet on intestinal permeability and inflammation in Crohn’s disease. Gastroenterology. 1991;101:84–89.PubMedGoogle Scholar
  12. 12.
    Keshavarzian A, Price YE, Peters AM, Lavender JP, Wright NA, Hodgson HJ. Specificity of indium-111 granulocyte scanning and fecal excretion measurement in inflammatory bowel disease—an autoradiographic study. Dig Dis Sci. 1985;30:1156–1160.CrossRefPubMedGoogle Scholar
  13. 13.
    Costa F, Mumolo MG, Ceccarelli L, et al. Calprotectin is a stronger predictive marker of relapse in ulcerative colitis than in Crohn’s disease. Gut. 2005;54:364–368.CrossRefPubMedGoogle Scholar
  14. 14.
    Miyamoto M, Prause O, Sjostrand M, Laan M, Lotvall J, Linden A. Endogenous IL-17 as a mediator of neutrophil recruitment caused by endotoxin exposure in mouse airways. J Immunol. 2003;170:4665–4672.PubMedGoogle Scholar
  15. 15.
    Laan M, Prause O, Miyamoto M, et al. A role of GM-CSF in the accumulation of neutrophils in the airways caused by IL-17 and TNF-alpha. Eur Respir J. 2003;21:387–393.CrossRefPubMedGoogle Scholar
  16. 16.
    Lee JW, Wang P, Kattah MG, et al. Differential regulation of chemokines by IL-17 in colonic epithelial cells. J Immunol. 2008;181:6536–6545.PubMedGoogle Scholar
  17. 17.
    Malmstrom V, Shipton D, Singh B, et al. CD134 l expression on dendritic cells in the mesenteric lymph nodes drives colitis in T cell-restored SCID mice. J Immunol. 2001;166:6972–6981.PubMedGoogle Scholar
  18. 18.
    Niess JH. Role of mucosal dendritic cells in inflammatory bowel disease. World J Gastroenterol. 2008;14:5138–5148.CrossRefPubMedGoogle Scholar
  19. 19.
    Hirano T. Interleukin-6 and its relation to inflammation and disease. Clin Immunol Immunopathol. 1992;62:S60–S65.CrossRefPubMedGoogle Scholar
  20. 20.
    Dorn I, Schlenke P, Mascher B, Stange EF, Seyfarth M. Lamina propria plasma cells in inflammatory bowel disease: intracellular detection of immunoglobulins using flow cytometry. Immunobiology. 2002;206:546–557.CrossRefPubMedGoogle Scholar
  21. 21.
    Siegmund B, Zeitz M. Clinical aspects of inflammatory bowel disease. Eur J Immunol. 2009;39:2026–2030.CrossRefPubMedGoogle Scholar
  22. 22.
    Heinsbroek SE, Gordon S. The role of macrophages in inflammatory bowel diseases. Expert Rev Mol Med. 2009;11:e14.CrossRefPubMedGoogle Scholar
  23. 23.
    Keel M, Ungethum U, Steckholzer U, et al. Interleukin-10 counterregulates proinflammatory cytokine-induced inhibition of neutrophil apoptosis during severe sepsis. Blood. 1997;90:3356–3363.PubMedGoogle Scholar
  24. 24.
    Wang ZQ, Bapat AS, Rayanade RJ, Dagtas AS, Hoffmann MK. Interleukin-10 induces macrophage apoptosis and expression of CD16 (FcgammaRIII) whose engagement blocks the cell death programme and facilitates differentiation. Immunology. 2001;102:331–337.CrossRefPubMedGoogle Scholar
  25. 25.
    Jungbeck M, Stopfer P, Bataille F, Nedospasov SA, Mannel DN, Hehlgans T. Blocking lymphotoxin beta receptor signalling exacerbates acute DSS-induced intestinal inflammation—opposite functions for surface lymphotoxin expressed by T and B lymphocytes. Mol Immunol. 2008;45:34–41.CrossRefPubMedGoogle Scholar
  26. 26.
    Lin ZQ, Kondo T, Ishida Y, Takayasu T, Mukaida N. Essential involvement of IL-6 in the skin wound-healing process as evidenced by delayed wound healing in IL-6-deficient mice. J Leukoc Biol. 2003;73:713–721.CrossRefPubMedGoogle Scholar
  27. 27.
    O’Connor W Jr, Kamanaka M, Booth CJ, et al. A protective function for interleukin 17a in T cell-mediated intestinal inflammation. Nat Immunol. 2009;10:603–609.CrossRefPubMedGoogle Scholar
  28. 28.
    Ogawa A, Andoh A, Araki Y, Bamba T, Fujiyama Y. Neutralization of interleukin-17 aggravates dextran sulfate sodium-induced colitis in mice. Clin Immunol. 2004;110:55–62.CrossRefPubMedGoogle Scholar
  29. 29.
    Dieleman LA, Ridwan BU, Tennyson GS, Beagley KW, Bucy RP, Elson CO. Dextran sulfate sodium-induced colitis occurs in severe combined immunodeficient mice. Gastroenterology. 1994;107:1643–1652.PubMedGoogle Scholar
  30. 30.
    Dieleman LA, Palmen MJ, Akol H, et al. Chronic experimental colitis induced by dextran sulphate sodium (DSS) is characterized by Th1 and Th2 cytokines. Clin Exp Immunol. 1998;114:385–391.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Lindsay J. Hall
    • 1
    Email author
  • Emilie Faivre
    • 1
  • Aoife Quinlan
    • 1
  • Fergus Shanahan
    • 1
  • Kenneth Nally
    • 1
  • Silvia Melgar
    • 1
    • 2
  1. 1.Alimentary Pharmabiotic Centre, Biosciences InstituteUniversity College CorkCorkIreland
  2. 2.Immuno-Inflammation, CEDDGlaxoSmithKlineStevenageUK

Personalised recommendations