Title: Role of interleukin-12 in the induction of mucosal inflammation and abrogation of regulatory T cell function in chronic experimental colitis
Authors: Liu, Z ×
Geboes, Karel
Heremans, Hubertine
Overbergh, Lutgart
Mathieu, Chantal
Rutgeerts, Paul
Ceuppens, Jan #
Issue Date: Jul-2001
Series Title: European Journal of Immunology vol:31 issue:5 pages:1550-60
Abstract: IL-12 promotes Th1 cell differentiation and cell-mediated immunity. In the present study, the potential role of IL-12 was analyzed in an experimental colitis model in scid mice reconstituted with syngeneic CD45RBhighCD4+ T cells. Real-time reverse transcription-PCR studies demonstrated that IL-12 p40 mRNA in inflamed colon is induced shortly after T cell transfer and maintained at a stable level after week 4, at the time when wasting disease starts. Administration of anti-IL-12 on days 0,14, and 28 (early treatment) or on days 28, 42, and 56 (delayed treatment) after T cell transfer, effectively prevented or, respectively cured wasting disease and colitis in scid recipients. Anti-IL-12 treatment abrogated mucosal inflammation with significantly diminished leukocyte infiltration (CD4 cells, macrophages) and CD54 expression, and down-regulated proinflammatory cytokines IFN-gamma and IL-2. Of note, although splenic CD4+ T cells are unable to induce disease as a result of the presence of regulatory CD45RBlow cells, splenic CD4+ T cells, preactivated by IL-12 and anti-CD3 in vitro, were highly pathogenic in inducing severe mucosal inflammation, suggesting that IL-12 and anti-CD3 abrogated regulatory T cell function. These findings indicate that IL-12 is important for the induction of experimental colitis through effects on proinflammatory cytokine production and on regulatory T cell function.
ISSN: 0014-2980
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Translational Research in GastroIntestinal Disorders
Translational Cell & Tissue Research
Clinical and Experimental Endocrinology
Laboratory of Clinical Immunology
Laboratory of Immunobiology (Rega Institute)
× corresponding author
# (joint) last author

Files in This Item:

There are no files associated with this item.

Request a copy


All items in Lirias are protected by copyright, with all rights reserved.

© Web of science