E Stüber1, A Von Freier, D Marinescu, U R Fölsch. 1. Department of Internal Medicine, I. Medizinische Universitätsklinik, Christian-Albechts-Universität, Kiel, Germany.
Abstract
BACKGROUND & AIMS: The intestinal histology of murine semiallogeneic graft-versus-host (GVH) disease is characterized by lymphocytic infiltrates, crypt hyperplasia, and villous atrophy. Mechanisms of T cell-mediated changes of the mucosal architecture were investigated. METHODS: The rate of cellular apoptosis and proliferation, changes in the composition of extracellular matrix (ECM), and the role of OX40-OX40L interactions in the pathogenesis of villous atrophy and crypt hyperplasia were examined. RESULTS: The rate of apoptosis and the number of proliferating cells were significantly increased in GVH animals compared with control animals. In addition, expression of tenascin, an ECM component, was down-regulated in GVH animals. Inhibition of OX40-OX40L interactions in GVH animals by administration of an OX40-Ig fusion protein completely prevented the development of crypt hyperplasia and villous atrophy in GVH animals. Tenascin expression was up-regulated in OX40-Ig-treated mice compared with GVH animals, suggesting an important function of this ECM component in mucosal repair. CONCLUSIONS: The OX40-OX40L interaction is crucial in the pathogenesis of GVH, a T cell-mediated intestinal disease. The data suggest that the ECM component tenascin is probably relevant for the regeneration and maintenance of intestinal tissue architecture.
BACKGROUND & AIMS: The intestinal histology of murine semiallogeneic graft-versus-host (GVH) disease is characterized by lymphocytic infiltrates, crypt hyperplasia, and villous atrophy. Mechanisms of T cell-mediated changes of the mucosal architecture were investigated. METHODS: The rate of cellular apoptosis and proliferation, changes in the composition of extracellular matrix (ECM), and the role of OX40-OX40L interactions in the pathogenesis of villous atrophy and crypt hyperplasia were examined. RESULTS: The rate of apoptosis and the number of proliferating cells were significantly increased in GVH animals compared with control animals. In addition, expression of tenascin, an ECM component, was down-regulated in GVH animals. Inhibition of OX40-OX40L interactions in GVH animals by administration of an OX40-Ig fusion protein completely prevented the development of crypt hyperplasia and villous atrophy in GVH animals. Tenascin expression was up-regulated in OX40-Ig-treated mice compared with GVH animals, suggesting an important function of this ECM component in mucosal repair. CONCLUSIONS: The OX40-OX40L interaction is crucial in the pathogenesis of GVH, a T cell-mediated intestinal disease. The data suggest that the ECM component tenascin is probably relevant for the regeneration and maintenance of intestinal tissue architecture.
Authors: Andrew D Weinberg; Nicholas P Morris; Magdalena Kovacsovics-Bankowski; Walter J Urba; Brendan D Curti Journal: Immunol Rev Date: 2011-11 Impact factor: 12.988
Authors: Israt S Alam; Federico Simonetta; Lukas Scheller; Aaron T Mayer; Robert Negrin; Sanjiv S Gambhir; Surya Murty; Ophir Vermesh; Tomomi W Nobashi; Juliane K Lohmeyer; Toshihito Hirai; Jeanette Baker; Kenneth H Lau Journal: Cancer Res Date: 2020-09-08 Impact factor: 12.701
Authors: T Kuroiwa; E Kakishita; T Hamano; Y Kataoka; Y Seto; N Iwata; Y Kaneda; K Matsumoto; T Nakamura; T Ueki; J Fujimoto; T Iwasaki Journal: J Clin Invest Date: 2001-06 Impact factor: 14.808