Innate immunity and inflammation in systemic sclerosis
- 1 November 2009
- journal article
- review article
- Published by Ovid Technologies (Wolters Kluwer Health) in Current Opinion in Rheumatology
- Vol. 21 (6), 617-622
- https://doi.org/10.1097/bor.0b013e32832fd69e
Abstract
Purpose of review Recent advances in our understanding of innate immunity and inflammation have direct bearing on how we understand autoimmunity, fibrosis and how innate immune sensors might stimulate both of these key features of systemic sclerosis (SSc) Recent findings Nucleic acid containing immune complexes activate toll-like receptors (TLRs) and induce expression of interferon responsive genes (IRGs) and autoantibodies in systemic lupus erythematosus (SLE). Recent studies indicate that increased SSc expression of IRGs may also be mediated by nucleic acid containing immune complexes. An expanding array of non-TLR innate immune pathways has recently been discovered. In particular, nalp3 mediated inflammasome activation of caspase-1 and conversion of pro-IL-1 to IL-1 play a key role in silica-mediated and bleomycin-mediated pulmonary fibrosis. TLR activation stimulates other inflammatory mediators, such as IL-1, IL-6 and TNFa in macrophages and dendritic cells. Activation of these and other inflammatory mediators, through TLR and non-TLR sensors, may cooperate to upregulate fibrotic mediators such as TGFβ and IL-13. Summary These observations provide a new paradigm for understanding the relationship between immunity/inflammation and fibrosis. New therapeutics, including TLR agonists and antagonists, and IFN inhibitors are currently under investigation. Further understandings of inflammasome-mediated fibrosis may provide further insights into SSc pathogenesis.Keywords
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