The fibroblast as a therapeutic target in rheumatoid arthritis

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Highlights▸ Therapies targeting fibroblasts in RA are a certainty. ▸ These therapies may succeed in treating existing biologic ‘non-responders’. ▸ Fibroblast therapies have the potential to modify disease persistence. ▸ Novel fibroblast markers developed in cancer and immunology will provide a new generation of specific treatments. ▸ More specific drugs that do not target leukocytes are likely to cause less bone marrow suppression and infection.Significant advances have been made in the last 5 years that have finally allowed investigators to start targeting stromal cells such as fibroblasts in inflammatory disease. Rheumatoid arthritis is a prototype inflammatory disease, in which fibroblasts maintain the persistence of inflammation in the joint underpinned by a unique pathological phenotype driven by multiple epigenetic modifications.The step changes that are enabling the development of such therapies are an improved understanding of the mechanisms by which fibroblasts mediate persistence and the discovery of new markers that identify discrete functional subsets of fibroblast cells that have potential as disease-specific therapeutic targets.

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