Apoptotic cell-based therapy to treat collagen-induced experimental arthritis (P5191)

Abstract

Abstract Biotherapies are emerging to treat rheumatoid arthritis (RA). Most of them target a cellular or soluble factor involved in the physiopathology of RA. Here we evaluated whether immunomodulatory properties of apoptotic cells can treat RA. Apoptotic cell approach has been successfully assessed to prevent arthritis development in experimental rat model, as well as in other inflammatory experimental settings. Thus we investigated apoptotic cell injection to treat RA in a mouse model of collagen-induced arthritis (CIA). Four to 8 days after CIA development in susceptible DBA/1, mice presenting arthritic symptoms were treated with apoptotic cells (5.10e6 cell/mouse). As control, methotrexate was used (MTX, 15 mg/kg, twice) alone or with apoptotic cells. Regulatory T cells (Treg) were assessed by FACS at time of sacrifice (day 40/45). Apoptotic cell injection demonstrated a significant decrease of arthritis score (p>0.01; 4 independent experiments), associated with an increased percentage of Treg in the spleen at time of sacrifice. MTX was sufficient to decrease arthritis as well and apoptotic cell injection did not influence MTX efficiency and vice-et-versa. Whereas MTX did not affect the percentage of Treg, MTX + apoptotic cell treatment induced a strong increase of Treg in the spleen and draining lymph nodes. Apoptotic cell injection is an effective treatment to reduce RA severity and should be consider in clinic as an alternative method for biotherapy refractory patients.