title: Artesunate abolishes germinal center B cells and inhibits autoimmune arthritis.
abstract: The antimalarial drug artemisinin and its derivatives exhibit potent immunosuppressive activity in several autoimmune disease models, however the mechanisms are not well-understood. This study was designed to investigate the therapeutic effects and the underlying mechanisms of the artemisinin analog artesunate using the K/BxN mouse model of rheumatoid arthritis. The well-studied disease mechanisms of K/BxN model allowed us to pinpoint the effect of artesunate on disease. Artesunate treatment prevented arthritis development in young K/BxN mice by inhibiting germinal center (GC) formation and production of autoantibodies. In adult K/BxN mice with established arthritis, artesunate diminished GC B cells in a few days. However, artesunate did not affect the follicular helper T cells (Tfh). In contrast to the spontaneous K/BxN model, artesunate treatment exerted minor influence on K/BxN serum transfer induced arthritis suggesting that artesunate has minimal effect on inflammatory responses downstream of antibody production. Finally, we showed that artesunate preferentially inhibits proliferating GC B cells. These results identify GC B cells as a target of artesunate and provide a new rationale for using artemisinin analogues to treat autoimmune diseases mediated by autoantibodies.
authors.affiliation: Department of Medicine and Knapp Center for Lupus and Immunology Research, University of Chicago, Chicago, Illinois, United States of America.
authors.forename: Lifei
authors.initials: L
authors.lastname: Hou
authors.affiliation: Committee on Immunology, University of Chicago, Chicago, Illinois, United States of America.
authors.forename: Katharine E
authors.initials: KE
authors.lastname: Block
authors.affiliation: Department of Medicine and Knapp Center for Lupus and Immunology Research, University of Chicago, Chicago, Illinois, United States of America.
authors.forename: Haochu
authors.initials: H
authors.lastname: Huang
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use*; D037621:Artemisinins / Q000627:therapeutic use*; D000077332:Artesunate; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000517:prevention & control; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D001402:B-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D018858:Germinal Center / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D011897:Random Allocation; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D000077332:Artesunate