Effects of different immunosuppressive regimens on regulatory T-cells in noninflamed colon of liver transplant recipients
Article first published online: 17 JAN 2007
Copyright © 2007 Crohn's & Colitis Foundation of America, Inc.
Inflammatory Bowel Diseases
Volume 13, Issue 6, pages 703–709, June 2007
How to Cite
Verdonk, R.C., Haagsma, E.B., Jonker, M.R., Bok, L.I.H., Zandvoort, J.H., Kleibeuker, J.H., Faber, K.N. and Dijkstra, G. (2007), Effects of different immunosuppressive regimens on regulatory T-cells in noninflamed colon of liver transplant recipients. Inflamm Bowel Dis, 13: 703–709. doi: 10.1002/ibd.20087
- Issue published online: 3 MAY 2007
- Article first published online: 17 JAN 2007
- Manuscript Accepted: 21 NOV 2006
- Manuscript Received: 20 NOV 2006
- Novartis Pharma BV, The Netherlands
- inflammatory bowel disease;
- regulatory T-cells;
- liver transplantation
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)