Innate immune system in RA

Pattern recognition receptors (PRRs) such as Toll-like receptors (TLRs) activate the innate immune system through recognition of microbial fragments. The existence of endogenous ligands however, suggests an additional role for PRRs in sensing general tissue damage. Activation of PRRs leads to up-regulation of pro-inflammatory cytokines, growth factors and chemokines and modulates adaptive immune responses by induction of co-stimulatory molecules, maturation of dendritic cells and stimulation of B-cells.
Expression, regulation and activation of TLRs in rheumatoid arthritis in particular in synovial fibroblasts is extensively studied by our group. Thereby, a prominent role of innate immune mechanisms in the pathogenesis of rheumatoid arthritis could be shown and synovial fibroblasts were identified as cells of the innate immune system which secrete a variety of chemokines, pro-inflammatory cytokines and matrix-degrading enzymes after stimulation of TLR pathways.

Publications

Kyburz D, Rethage J, Seibl R, Lauener R, Gay RE, Carson DA, Gay S. Bacterial peptidoglycans but not CpG oligodeoxynucleotides activate synovial fibroblasts by toll-like receptor signaling. Arthritis Rheum 2003, 48:642-50.

Pierer M, Rethage J, Seibl R, Lauener R, Brentano F, Wagner U, Hantzschel H, Michel BA, Gay RE, Gay S, Kyburz D. Chemokine secretion of rheumatoid arthritis synovial fibroblasts stimulated by Toll-like receptor 2 ligands. J Immunol 2004, 172:1256-65.

Brentano F, Schorr O, Gay RE, Gay S, Kyburz D. RNA released from necrotic synovial fluid cells activates rheumatoid arthritis synovial fibroblasts via Toll-like receptor 3. Arthritis Rheum 2005, 52:2656-65.

Druckversion