Effects of different immunosuppressive regimens on regulatory T-cells in noninflamed colon of liver transplant recipients

R. C. Verdonk*, E. B. Haagsma, M. R. Jonker, J. H. Zandvoort, J. H. Kleibeuker, K. N. Faber, G. Dijkstra

*Corresponding author voor dit werk

OnderzoeksoutputAcademicpeer review

23 Citaten (Scopus)

Samenvatting

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-beta (TGF-beta) and interleukin-10 (IL-10) were studied by quantitative polymerase chain reaction (Q-PCR) and immunohistochemistry. TGF-beta-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-beta, and Smad expression. Mucosal Foxp3 mRNA levels and Foxp3+CD3+ cells were significantly 4 reduced in transplant recipients using prednisone/azathioprine/tacrolimus compared with controls but no direct relationship between Foxp3 expression and I specific drug was detected.

Conclusions: These results challenge the hypothesis that calcineurin-induced reduction of Treg or TGF-beta expression predisposes nontransplanted tissue to inflammation, but indicate that combined immunosuppression hampers Treg development in the intestine.

Originele taal-2English
Pagina's (van-tot)703-709
Aantal pagina's7
TijdschriftInflammatory Bowel Diseases
Volume13
Nummer van het tijdschrift6
DOI's
StatusPublished - jun.-2007

Vingerafdruk

Duik in de onderzoeksthema's van 'Effects of different immunosuppressive regimens on regulatory T-cells in noninflamed colon of liver transplant recipients'. Samen vormen ze een unieke vingerafdruk.

Citeer dit