Journal article

Therapeutic Effects of a TANK-Binding Kinase 1 Inhibitor in Germinal Center-Driven Collagen-Induced Arthritis

Cynthia Louis, Devi Ngo, Damian B D'Silva, Jacinta Hansen, Louisa Phillipson, Helene Jousset, Patrizia Novello, David Segal, Kate E Lawlor, Christopher J Burns, Ian P Wicks



OBJECTIVE: The production of class-switched high-affinity autoantibodies derived from organized germinal centers (GCs) is a hallmark of many autoimmune inflammatory diseases, including rheumatoid arthritis (RA). TANK-binding kinase 1 (TBK-1) is a serine/threonine kinase involved in the maturation of GC follicular helper T (Tfh) cells downstream of inducible costimulator signaling. We undertook this study to assess the therapeutic potential of TBK-1 inhibition using the small-molecule inhibitor WEHI-112 in antibody-dependent models of inflammatory arthritis. METHODS: Using the models of collagen-induced arthritis (CIA), antigen-induced arthritis (AIA), and K/BxN serum-transfer-induced arthrit..

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