BACKGROUND AND AIMS: Although CD30 has long been recognized as an important marker in many lymphomas of diverse origin, and as an activation molecule on B and T cells, its primary function has remained obscure. Soluble CD30 (sCD30) is released from CD30 on the cell membrane by enzymatic cleavage. This study investigated the role of CD30 ligand (CD30L)/CD30 signals in intestinal mucosal damage. METHODS: Serum sCD30 in patients with ulcerative colitis (UC) and Crohn's disease (CD) and healthy individuals was assessed. A model of enteritis induced by anti-CD3 monoclonal antibody injection was studied in wild-type mice and in CD30L knockout mice. RESULTS: Increased sCD30 was observed in UC and CD patients, and the level was correlated with disease activity in both conditions. In a murine model of enteritis, histological intestinal damage was significantly reduced in CD30L knockout mice with decreased Th1 and Th17 cytokine levels. Moreover, blocking of CD30L/CD30 signals by CD30-immunoglobulin (CD30-Ig) resulted in reduced inflammation. CONCLUSIONS: Increased sCD30 expression correlating with disease activity suggested that CD30L/CD30 signals play an important role in pathogenesis of UC and CD. CD30L/CD30 pathway acts as an accelerator of enteritis in a murine disease model. Successful blockade of enteritis by CD30-Ig suggests a potential tool for future therapy of inflammatory bowel diseases.
BACKGROUND AND AIMS: Although CD30 has long been recognized as an important marker in many lymphomas of diverse origin, and as an activation molecule on B and T cells, its primary function has remained obscure. Soluble CD30 (sCD30) is released from CD30 on the cell membrane by enzymatic cleavage. This study investigated the role of CD30 ligand (CD30L)/CD30 signals in intestinal mucosal damage. METHODS: Serum sCD30 in patients with ulcerative colitis (UC) and Crohn's disease (CD) and healthy individuals was assessed. A model of enteritis induced by anti-CD3 monoclonal antibody injection was studied in wild-type mice and in CD30L knockout mice. RESULTS: Increased sCD30 was observed in UC and CD patients, and the level was correlated with disease activity in both conditions. In a murine model of enteritis, histological intestinal damage was significantly reduced in CD30L knockout mice with decreased Th1 and Th17 cytokine levels. Moreover, blocking of CD30L/CD30 signals by CD30-immunoglobulin (CD30-Ig) resulted in reduced inflammation. CONCLUSIONS: Increased sCD30 expression correlating with disease activity suggested that CD30L/CD30 signals play an important role in pathogenesis of UC and CD. CD30L/CD30 pathway acts as an accelerator of enteritis in a murine disease model. Successful blockade of enteritis by CD30-Ig suggests a potential tool for future therapy of inflammatory bowel diseases.
Authors: R Giacomelli; A Passacantando; I Parzanese; P Vernia; N Klidara; F Cucinelli; R Lattanzio; E Santori; P Cipriani; R Caprilli; G Tonietti Journal: Clin Exp Immunol Date: 1998-03 Impact factor: 4.330
Authors: Bruce R Blazar; Robert B Levy; Tak W Mak; Angela Panoskaltsis-Mortari; Hiromi Muta; Monica Jones; Melinda Roskos; Jonathan S Serody; Hideo Yagita; Eckhard R Podack; Patricia A Taylor Journal: J Immunol Date: 2004-09-01 Impact factor: 5.422
Authors: C A Smith; H J Gruss; T Davis; D Anderson; T Farrah; E Baker; G R Sutherland; C I Brannan; N G Copeland; N A Jenkins Journal: Cell Date: 1993-07-02 Impact factor: 41.582
Authors: M Merger; J L Viney; R Borojevic; D Steele-Norwood; P Zhou; D A Clark; R Riddell; R Maric; E R Podack; K Croitoru Journal: Gut Date: 2002-08 Impact factor: 23.059