Fig. 1

Efficacy of Janus kinase (JAK) + spleen tyrosine kinase (SYK) inhibition as a preventive treatment in glucose-6-phosphate isomerase (G6PI)-induced arthritis. DBA/1 mice were immunized with G6PI + complete Freund’s adjuvant on day 0, after T regulatory cell depletion with anti-CD25 Ab (days −8 and −11). Treatments (20 mg/kg of tofacitinib - JAK inhibitor (JAKi) - and/or 30 mg/kg of PRT062607 – SYK inhibitor (SYKi)) were orally administered daily from day 0. Samples were obtained on day 31 unless otherwise specified. a Time course for arthritis scores and resulting areas under these score curves. b Mean weight of both inguinal lymph nodes at day 6 and day 31 post-immunization. c Numbers of CD11c^hiMHCII⁺CD86⁺ activated dendritic cells (DCs) in the spleen. d Cytokine secretion by splenocytes stimulated in vitro with 20 μg/ml recomninant human G6PI for 72 h. e Numbers of CD19⁺MHCII⁺CD86⁺ activated B cells in the spleen. f Levels of G6PI-specific IgGs in plasma. g Histological features of G6PI-induced arthritis, including severe inflammation and bone/cartilage destruction of tarsal and phalangeal joints from hind paws (H&E staining). Arrows cell aggregates (left, bar 500 μM), infiltration of lymphocytes, macrophages and neutrophils in the synovium (middle, bar 200 μM) and osteoclasts (right, bar 50 μM). h and i Data and representative histological sections of tarsal joints (bar 500 μM). Graphs show mean (+ standard error of the mean) for 3–5 mice/group, *p <0.05 versus vehicle control, ^# p <0.05 versus non-immunized and untreated group (naive). N naive, V/Veh vehicle, IFN interferon