Arthritis Rheumatol 2021 Aug 23. Epub 2021 Aug 23.
Inflammation and Immunology Research Unit, Pfizer, Inc, 1 Portland St, Cambridge, MA, 02139, USA.
Objective: Use a highly potent and selective small molecule inhibitor of interleukin-1 associated kinase (IRAK) 4, PF-06650833, to demonstrate its role in autoimmune pathophysiology in vitro, in vivo and in the clinic.
Methods: Rheumatoid arthritis (RA) inflammatory pathophysiology was modeled in vitro through stimulation of primary human macrophages (MΦ) with anti-citrullinated protein antibody (ACPA) immune complexes (IC), RA fibroblast-like synoviocyte (-FLS) cultures stimulated with toll-like receptor (TLR) ligands, as well as additional human primary cell co-cultures. Systemic lupus erythematosus (SLE) pathophysiology was simulated in human neutrophils, dendritic cells (DC), B cells and PBMC stimulated with TLR ligands and SLE patient IC. Read More