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Involvement of OX40-OX40L interactions in the intestinal manifestations of the murine acute graft-versus-host disease.
- Source :
-
Gastroenterology [Gastroenterology] 1998 Nov; Vol. 115 (5), pp. 1205-15. - Publication Year :
- 1998
-
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.<br />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.<br />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.<br />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.
- Subjects :
- Acute Disease
Animals
Apoptosis physiology
Cell Division physiology
Epithelial Cells physiology
Extracellular Matrix Proteins metabolism
Graft vs Host Disease pathology
Immunoglobulins physiology
Intestine, Small pathology
Intestines pathology
Jejunum pathology
Jejunum physiopathology
Kinetics
Mice
Mice, Inbred C57BL
Mice, Inbred DBA
OX40 Ligand
Receptors, OX40
Receptors, Tumor Necrosis Factor physiology
Regeneration physiology
Tumor Necrosis Factor Receptor Superfamily, Member 7 immunology
Tumor Necrosis Factor Receptor Superfamily, Member 7 physiology
Tumor Necrosis Factors
Graft vs Host Disease physiopathology
Intestines physiopathology
Membrane Glycoproteins
Subjects
Details
- Language :
- English
- ISSN :
- 0016-5085
- Volume :
- 115
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Gastroenterology
- Publication Type :
- Academic Journal
- Accession number :
- 9797376
- Full Text :
- https://doi.org/10.1016/s0016-5085(98)70092-7