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
ARTHRITIS & RHEUMATOLOGY | WILEY | Published : 2019
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..View full abstract
Awarded by National Health and Medical Research Council of Australia
Supported by the Reid Charitable Trusts, Victorian Government Operational Infrastructure Support, Australian Cancer Research Foundation, and the National Health and Medical Research Council of Australia (Clinical Practitioner Fellowship 1023407, program grant 1016647, development grant 1055374, and IRIISS grant 9000220). Dr. Burns is a Dunn Fellow of Dyson Bequest Funding.