Journal of Molecular Histology

, Volume 45, Issue 2, pp 217–227 | Cite as

Disturbance of intraepithelial lymphocytes in a murine model of acute intestinal ischemia/reperfusion

  • Yuan Qiu
  • Min Yu
  • Yang Yang
  • Halei Sheng
  • Wensheng Wang
  • Lihua Sun
  • Guoqing Chen
  • Yong Liu
  • Weidong Xiao
  • Hua Yang
Original Paper

Abstract

Strategically located at the epithelial basolateral surface, intraepithelial lymphocytes (IELs) are intimately associated with epithelial cells and maintain the epithelial barrier integrity. Intestinal ischemia–reperfusion (I/R)-induced acute injury not only damages the epithelium but also affects the mucosal barrier function. Therefore, we hypothesized that I/R-induced mucosal damage would affect IEL phenotype and function. Adult C57BL/6J mice were treated with intestinal I/R or sham. Mice were euthanized at 6 h after I/R, and the small bowel was harvested for histological examination and to calculate the transmembrane resistance. Occludin expression and IEL location were detected through immunohistochemistry. The IEL phenotype, activation, and apoptosis were examined using flow cytometry. Cytokine and anti-apoptosis-associated gene expressions were measured through RT-PCR. Intestinal I/R induced the destruction of epithelial cells and intercellular molecules (occludin), resulting in IEL detachment from the epithelium. I/R also significantly increased the CD8αβ, CD4, and TCRαβ IEL subpopulations and significantly changed IEL-derived cytokine expression. Furthermore, I/R enhanced activation and promoted apoptosis in IELs. I/R-induced acute intestinal mucosal damage significantly affected IEL phenotype and function. These findings provide profound insight into potential IEL-mediated epithelial barrier dysfunction after intestinal I/R.

Keywords

Ischemia–reperfusion Injury Intestinal epithelium Intraepithelial lymphocytes 

References

  1. Abadie V, Discepolo V, Jabri B (2012) Intraepithelial lymphocytes in celiac disease immunopathology. Semin Immunopathol 34:551–566PubMedCrossRefGoogle Scholar
  2. (2000) American gastroenterological association medical position statement: guidelines on intestinal ischemia.Gastroenterology 118:951–953 Google Scholar
  3. Balzan S, de Almeida Quadros C, de Cleva R, Zilberstein B, Cecconello I (2007) Bacterial translocation: overview of mechanisms and clinical impact. J Gastroenterol Hepatol 22:464–471PubMedCrossRefGoogle Scholar
  4. Cai Y, Wang W, Liang H, Sun L, Teitelbaum DH, Yang H (2012a) Keratinocyte growth factor improves epithelial structure and function in a mouse model of intestinal ischemia/reperfusion. PLoS ONE 7:e44772PubMedCentralPubMedCrossRefGoogle Scholar
  5. Cai YJ, Wang WS, Liang HY, Sun LH, Teitelbaum DH, Yang H (2012b) Keratinocyte growth factor up-regulates Interleukin-7 expression following intestinal ischemia/reperfusion in vitro and in vivo. Int J Clin Exp Pathol 5:569–580PubMedCentralPubMedGoogle Scholar
  6. Cerqueira NF, Hussni CA, Yoshida WB (2005) Pathophysiology of mesenteric ischemia/reperfusion: a review. Acta Cir Bras 20:336–343PubMedGoogle Scholar
  7. Chassin C, Hempel C, Stockinger S, Dupont A, Kubler JF, Wedemeyer J, Vandewalle A, Hornef MW (2012) MicroRNA-146a-mediated downregulation of IRAK1 protects mouse and human small intestine against ischemia/reperfusion injury. EMBO Mol Med 4:1308–1319PubMedCentralPubMedCrossRefGoogle Scholar
  8. Cheroutre H, Lambolez F, Mucida D (2011) The light and dark sides of intestinal intraepithelial lymphocytes. Nat Rev Immunol 11:445–456PubMedCentralPubMedCrossRefGoogle Scholar
  9. Di Sabatino A, Ciccocioppo R, Cupelli F, Cinque B, Millimaggi D, Clarkson MM, Paulli M, Cifone MG, Corazza GR (2006) Epithelium derived interleukin 15 regulates intraepithelial lymphocyte Th1 cytokine production, cytotoxicity, and survival in coeliac disease. Gut 55:469–477PubMedCentralPubMedCrossRefGoogle Scholar
  10. Edelblum KL, Shen L, Weber CR, Marchiando AM, Clay BS, Wang Y, Prinz I, Malissen B, Sperling AI, Turner JR (2012) Dynamic migration of gammadelta intraepithelial lymphocytes requires occludin. Proc Natl Acad Sci U S A 109:7097–7102PubMedCentralPubMedCrossRefGoogle Scholar
  11. Guzel A, Kanter M, Pergel A, Erboga M (2012) Anti-inflammatory and antioxidant effects of infliximab on acute lung injury in a rat model of intestinal ischemia/reperfusion. J Mol Histol 43:361–369PubMedCrossRefGoogle Scholar
  12. Inagaki-Ohara K, Sawaguchi A, Suganuma T, Matsuzaki G, Nawa Y (2005) Intraepithelial lymphocytes express junctional molecules in murine small intestine. Biochem Biophys Res Commun 331:977–983PubMedCrossRefGoogle Scholar
  13. Inagaki-Ohara K, Dewi FN, Hisaeda H, Smith AL, Jimi F, Miyahira M, Abdel-Aleem AS, Horii Y, Nawa Y (2006) Intestinal intraepithelial lymphocytes sustain the epithelial barrier function against Eimeria vermiformis infection. Infect Immun 74:5292–5301PubMedCentralPubMedCrossRefGoogle Scholar
  14. Kontoyiannis D, Kotlyarov A, Carballo E, Alexopoulou L, Blackshear PJ, Gaestel M, Davis R, Flavell R, Kollias G (2001) Interleukin-10 targets p38 MAPK to modulate ARE-dependent TNF mRNA translation and limit intestinal pathology. EMBO J 20:3760–3770PubMedCentralPubMedCrossRefGoogle Scholar
  15. Kunisawa J, Takahashi I, Kiyono H (2007) Intraepithelial lymphocytes: their shared and divergent immunological behaviors in the small and large intestine. Immunol Rev 215:136–153PubMedCrossRefGoogle Scholar
  16. Lee WY, Hu YM, Ko TL, Yeh SL, Yeh CL (2012) Glutamine modulates sepsis-induced changes to intestinal intraepithelial gammadeltaT lymphocyte expression in mice. Shock 38:288–293PubMedCrossRefGoogle Scholar
  17. Li Q, Zhang Q, Wang M, Zhao S, Ma J, Luo N, Li N, Li Y, Xu G, Li J (2008) Interferon-gamma and tumor necrosis factor-alpha disrupt epithelial barrier function by altering lipid composition in membrane microdomains of tight junction. Clin Immunol 126:67–80PubMedCrossRefGoogle Scholar
  18. Madsen KL, Lewis SA, Tavernini MM, Hibbard J, Fedorak RN (1997) Interleukin 10 prevents cytokine-induced disruption of T84 monolayer barrier integrity and limits chloride secretion. Gastroenterology 113:151–159PubMedCrossRefGoogle Scholar
  19. Maretta M, Toth S, Bujdos M, Toth S Jr, Jonecova Z, Vesela J (2012) Alterations of epithelial layer after ischemic preconditioning of small intestine in rats. J Mol Histol 43:171–178PubMedCrossRefGoogle Scholar
  20. Montufar-Solis D, Garza T, Klein JR (2007) T-cell activation in the intestinal mucosa. Immunol Rev 215:189–201PubMedCentralPubMedCrossRefGoogle Scholar
  21. Mosley RL, Klein JR (1992) A rapid method for isolating murine intestine intraepithelial lymphocytes with high yield and purity. J Immunol Methods 156:19–26PubMedCrossRefGoogle Scholar
  22. Pergel A, Kanter M, Yucel AF, Aydin I, Erboga M, Guzel A (2011) Anti-inflammatory and antioxidant effects of infliximab in a rat model of intestinal ischemia/reperfusion injury. Toxicol Ind Health 28:923–932PubMedCrossRefGoogle Scholar
  23. Saccani F, Anselmi L, Jaramillo I, Bertoni S, Barocelli E, Sternini C (2012) Protective role of mu opioid receptor activation in intestinal inflammation induced by mesenteric ischemia/reperfusion in mice. J Neurosci Res 90:2146–2153PubMedCrossRefGoogle Scholar
  24. Shalapour S, Deiser K, Kuhl AA, Glauben R, Krug SM, Fischer A, Sercan O, Chappaz S, Bereswill S, Heimesaat MM, Loddenkemper C, Fromm M, Finke D, Hammerling GJ, Arnold B, Siegmund B, Schuler T (2012) Interleukin-7 links T lymphocyte and intestinal epithelial cell homeostasis. PLoS ONE 7:e31939PubMedCentralPubMedCrossRefGoogle Scholar
  25. Shen L (2012) Tight junctions on the move: molecular mechanisms for epithelial barrier regulation. Ann N Y Acad Sci 1258:9–18PubMedCentralPubMedCrossRefGoogle Scholar
  26. Simpson SJ, Hollander GA, Mizoguchi E, Allen D, Bhan AK, Wang B, Terhorst C (1997) Expression of pro-inflammatory cytokines by TCR alpha beta + and TCR gamma delta + T cells in an experimental model of colitis. Eur J Immunol 27:17–25PubMedCrossRefGoogle Scholar
  27. Suzuki K, Oida T, Hamada H, Hitotsumatsu O, Watanabe M, Hibi T, Yamamoto H, Kubota E, Kaminogawa S, Ishikawa H (2000) Gut cryptopatches: direct evidence of extrathymic anatomical sites for intestinal T lymphopoiesis. Immunity 13:691–702PubMedCrossRefGoogle Scholar
  28. Vidali F, Di Sabatino A, Broglia F, Cazzola P, Biancheri P, Viera FT, Vanoli A, Alvisi C, Perego M, Corazza GR (2010) Increased CD8+ intraepithelial lymphocyte infiltration and reduced surface area to volume ratio in the duodenum of patients with ulcerative colitis. Scand J Gastroenterol 45:684–689PubMedCrossRefGoogle Scholar
  29. Vollmar B, Menger MD (2011) Intestinal ischemia/reperfusion: microcirculatory pathology and functional consequences. Langenbecks Arch Surg 396:13–29PubMedCrossRefGoogle Scholar
  30. Yang H, Fan Y, Teitelbaum DH (2003a) Intraepithelial lymphocyte-derived interferon-gamma evokes enterocyte apoptosis with parenteral nutrition in mice. Am J Physiol Gastrointest Liver Physiol 284:G629–G637PubMedGoogle Scholar
  31. Yang H, Finaly R, Teitelbaum DH (2003b) Alteration in epithelial permeability and ion transport in a mouse model of total parenteral nutrition. Crit Care Med 31:1118–1125PubMedCrossRefGoogle Scholar
  32. Yang H, Spencer AU, Teitelbaum DH (2005) Interleukin-7 administration alters intestinal intraepithelial lymphocyte phenotype and function in vivo. Cytokine 31:419–428PubMedCrossRefGoogle Scholar
  33. Yang H, Sun X, Haxhija EQ, Teitelbaum DH (2007) Intestinal epithelial cell-derived interleukin-7: a mechanism for the alteration of intraepithelial lymphocytes in a mouse model of total parenteral nutrition. Am J Physiol Gastrointest Liver Physiol 292:G84–G91PubMedCentralPubMedCrossRefGoogle Scholar
  34. Yang H, Gumucio DL, Teitelbaum DH (2008a) Intestinal specific overexpression of interleukin-7 attenuates the alternation of intestinal intraepithelial lymphocytes after total parenteral nutrition administration. Ann Surg 248:849–856PubMedCentralPubMedCrossRefGoogle Scholar
  35. Yang H, Madison B, Gumucio DL, Teitelbaum DH (2008b) Specific overexpression of IL-7 in the intestinal mucosa: the role in intestinal intraepithelial lymphocyte development. Am J Physiol Gastrointest Liver Physiol 294:G1421–G1430PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Yuan Qiu
    • 1
  • Min Yu
    • 1
  • Yang Yang
    • 1
  • Halei Sheng
    • 2
  • Wensheng Wang
    • 1
  • Lihua Sun
    • 1
  • Guoqing Chen
    • 1
  • Yong Liu
    • 1
  • Weidong Xiao
    • 1
  • Hua Yang
    • 1
  1. 1.Department of General Surgery, Xinqiao HospitalThird Military Medical UniversityChongqingChina
  2. 2.Center of Medical Experiment and Technology, Xinqiao HospitalThird Military Medical UniversityChongqingChina

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