Effects of different immunosuppressive regimens on regulatory T-cells in noninflamed colon of liver transplant recipients
Corresponding Author
R.C. Verdonk MD
Department of Gastroenterology and Hepatology, University Medical Center Groningen, Groningen, The Netherlands
University Medical Center Groningen, Department of Gastroenterology and Hepatology, PO Box 30.001, Hanzeplein 1, 9700 RB, Groningen, The NetherlandsSearch for more papers by this authorE.B. Haagsma MD, PhD
Department of Gastroenterology and Hepatology, University Medical Center Groningen, Groningen, The Netherlands
Search for more papers by this authorM.R. Jonker
Department of Pathology and Laboratory Medicine, University Medical Center Groningen, Groningen, The Netherlands
Search for more papers by this authorL.I.H. Bok
Department of Gastroenterology and Hepatology, University Medical Center Groningen, Groningen, The Netherlands
Search for more papers by this authorJ.H. Zandvoort PhD
Department of Pathology and Laboratory Medicine, University Medical Center Groningen, Groningen, The Netherlands
Search for more papers by this authorJ.H. Kleibeuker MD, PhD
Department of Gastroenterology and Hepatology, University Medical Center Groningen, Groningen, The Netherlands
Search for more papers by this authorK.N. Faber PhD
Department of Gastroenterology and Hepatology, University Medical Center Groningen, Groningen, The Netherlands
Search for more papers by this authorG. Dijkstra MD, PhD
Department of Gastroenterology and Hepatology, University Medical Center Groningen, Groningen, The Netherlands
Search for more papers by this authorCorresponding Author
R.C. Verdonk MD
Department of Gastroenterology and Hepatology, University Medical Center Groningen, Groningen, The Netherlands
University Medical Center Groningen, Department of Gastroenterology and Hepatology, PO Box 30.001, Hanzeplein 1, 9700 RB, Groningen, The NetherlandsSearch for more papers by this authorE.B. Haagsma MD, PhD
Department of Gastroenterology and Hepatology, University Medical Center Groningen, Groningen, The Netherlands
Search for more papers by this authorM.R. Jonker
Department of Pathology and Laboratory Medicine, University Medical Center Groningen, Groningen, The Netherlands
Search for more papers by this authorL.I.H. Bok
Department of Gastroenterology and Hepatology, University Medical Center Groningen, Groningen, The Netherlands
Search for more papers by this authorJ.H. Zandvoort PhD
Department of Pathology and Laboratory Medicine, University Medical Center Groningen, Groningen, The Netherlands
Search for more papers by this authorJ.H. Kleibeuker MD, PhD
Department of Gastroenterology and Hepatology, University Medical Center Groningen, Groningen, The Netherlands
Search for more papers by this authorK.N. Faber PhD
Department of Gastroenterology and Hepatology, University Medical Center Groningen, Groningen, The Netherlands
Search for more papers by this authorG. Dijkstra MD, PhD
Department of Gastroenterology and Hepatology, University Medical Center Groningen, Groningen, The Netherlands
Search for more papers by this authorAbstract
Background: Regulatory T-cells (Treg) are natural suppressors of autoimmunity. Previous studies indicate that immunosuppressive drugs, especially calcineurin-inhibitors, may interfere with Treg homeostasis. Inflammatory bowel disease (IBD) can relapse or develop de novo after liver transplantation. IBD is associated with a relative deficiency of Treg. The aim of this study was to determine the effect of long-term immunosuppression on the presence of Treg in the noninflamed colonic mucosa of liver transplant recipients.
Methods: Colonic biopsies of normal mucosa of 36 liver transplant recipients on different types of immunosuppression and 11 controls were studied. Treg marker Foxp3 and Treg products transforming growth factor-β (TGF-β) and interleukin-10 (IL-10) were studied by quantitative polymerase chain reaction (Q-PCR) and immunohistochemistry. TGF-β-induced Smad-protein 3 and 7 were studied by Q-PCR.
Results: No significant differences between controls and patients were observed in IL-10, TGF-β, and Smad expression. Mucosal Foxp3 mRNA levels and Foxp3+CD3+ cells were significantly reduced in transplant recipients using prednisone/azathioprine/tacrolimus compared with controls but no direct relationship between Foxp3 expression and 1 specific drug was detected.
Conclusions: These results challenge the hypothesis that calcineurin-induced reduction of Treg or TGF-β expression predisposes nontransplanted tissue to inflammation, but indicate that combined immunosuppression hampers Treg development in the intestine.
(Inflamm Bowel Dis 2007)
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