Mesenchymal cell targeting by TNF as a common pathogenic principle in chronic inflammatory joint and intestinal diseases

• DOI: 10.1084/jem.20070906
• Publication Date: 2008-02-05T01:47:26Z
• Authors: Maria Armaka; Maria Apostolaki; Peggy Jacques; Dimitris L. Konto...; Dirk Elewaut; George Kollias
• Keywords: Inflammation; 0301 basic medicine; Arthritis; Mesenchymal Stem Cells; Mice, Transgenic; Sacroiliac Joint; Fibroblasts; 3. Good health; Mice, Inbred C57BL; Intestinal Diseases; Mice; 03 medical and health sciences; Ileum; Receptors, Tumor Necrosis Factor, Type I; Tumor Necrosis Factors; Brief Definitive Reports; Animals; Cells, Cultured; Bone Marrow Transplantation

Tumor necrosis factor (TNF) is key to the pathogenesis of various arthritic diseases and inflammatory bowel disease (IBD). Anti-TNF therapies have proved successful in clinical treatment these diseases, but a mechanistic understanding TNF function still lacking. We investigated early cellular mechanisms using an established transgenic model, which develops spondyloarthritis-like characterized by peripheral joint arthritis, sacroiliitis, enthesitis, Crohn's-like IBD. Bone marrow grafting experiments demonstrated that development arthritis requires receptor I (TNFRI) expression radiation-resistant compartment, also known be sufficient target IBD same model. Early activation synovial fibroblasts intestinal myofibroblasts could perturbed matrix metalloproteases their inhibitors. Notably, selective Cre/loxP-mediated TNFRI mesenchymal cells resulted fully arthritic–spondyloarthritic phenotype, indicating are primary targets pathologies. Our results offer novel perspective for gut pathologies indicate common pathways may explain often observed synovial–gut axis human disease.