[R01] Cellular and molecular mechanisms of IL-17A in the pathogenesis of psoriatic arthritis
Ente: National Institute of Arthritis and Musculoskeletal and Skin Diseases
Scadenza: 2030-03-31
Importo max: 567.663 EUR
Paese: US
Descrizione
Project Summary/Abstract
Psoriatic arthritis is a chronic and progressive inflammatory arthritis closely linked with psoriasis.
Blockade of the IL-17 signaling pathway shows impressive efficacy and excellent safety for
treatment of psoriasis but less so for PsA. Tissue penetrance limits the bioavailability of
monoclonal antibodies to the joint and fibrocartilaginous enthesis and IL-17A signaling is
diversified by local immune cells in tissues rendering IL-17A inhibition less effective. A higher
dosage poses the risks of serious infections and certain types of cancer as all IL-17 inhibitors are
immunosuppressive therefore to improve clinical outcomes in PsA more selective targeting is
required. Herein, we have developed a novel animal model of IL-17A gene transfer where mice
develop joint and skin inflammation associated with enthesitis, fingernail psoriasis and
onycholysis hallmarks of PsA pathology. We will interrogate our murine model to define the early
cellular and molecular pathways that dictate IL-17A-induced pathologies using state-of-the-art
transgenic mice and molecular tools. Our work will uncover the pathogenic mechanisms of IL-17A
and uncover novel molecular targets that can be exploited for therapeutic intervention and directly
benefit PsA patients worldwide.
Istituzione: UNIVERSITY OF ARIZONA
PI: Iannis Elias Adamopoulos
Progetto: 7R01AR084848-02
Settori: National Institute of Arthritis and Musculoskeletal and Skin Diseases
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