title: Artemisinin analogue SM934 attenuate collagen-induced arthritis by suppressing T follicular helper cells and T helper 17 cells.
abstract: SM934 is an artemisinin analogue with immunosuppressive properties and potent therapeutic activity against lupus-like diseases in autoimmune mice. In this report, the therapeutic efficacy and underlying mechanisms of SM934 on rheumatoid arthritis (RA) was investigated using collagen-induced arthritis (CIA) in DBA/1J mice. We demonstrated that SM934 treatment alleviate the severity of arthritis in CIA mice with established manifestations. The therapeutic benefits were associated with ameliorated joint swelling and reduced extent of bone erosion and destruction. Further, administration of SM934 diminished the development of T follicular helper (Tfh) cells and Th17 cells and suppressed the production of pathogenic antibodies, without altering the proportion of germinal center B cells. Ex vivo, SM934 treatment inhibited the bovine type II collagen (CII) induced proliferation and inflammatory cytokines secretion of CII -reactive T cells. In vitro, SM934 impeded the polarization of naïve CD4+T cells into Tfh cells and the expression of its transcript factor Bcl-6. Moreover, SM934 decreased the IL-21-producing CD4+T cells and dampened the IL-21 downstream signaling through STAT3. These finding offered the convincing evidence that artemisinin derivative might attenuate RA by simultaneously interfering with the generation of Tfh cells and Th17 cells as well as the subsequent antibody-mediated immune responses.
authors.affiliation: Laboratory of Immunology and Virology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, People's Republic of China.|Laboratory of Immunopharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, People's Republic of China.
authors.forename: Ze-Min
authors.initials: ZM
authors.lastname: Lin
authors.affiliation: Laboratory of Immunopharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, People's Republic of China.
authors.forename: Xiao-Qian
authors.initials: XQ
authors.lastname: Yang
authors.affiliation: Laboratory of Immunopharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, People's Republic of China.
authors.forename: Feng-Hua
authors.initials: FH
authors.lastname: Zhu
authors.affiliation: Laboratory of Immunopharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, People's Republic of China.
authors.forename: Shi-Jun
authors.initials: SJ
authors.lastname: He
authors.affiliation: Laboratory of Immunopharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Tang
authors.affiliation: Laboratory of Immunology and Virology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, People's Republic of China.|Laboratory of Immunopharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, People's Republic of China.
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Zuo
mesh_terms: D000818:Animals; D037621:Artemisinins / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000188:drug therapy / Q000191:economics* / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D002417:Cattle; D024043:Collagen Type II / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D007371:Interferon-gamma / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D051560:Proto-Oncogene Proteins c-bcl-6 / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D058504:Th17 Cells / Q000187:drug effects* / Q000378:metabolism; D000098546:Interleukin-21
chemical_list: D037621:Artemisinins; D024043:Collagen Type II; D007378:Interleukins; D051560:Proto-Oncogene Proteins c-bcl-6; D050796:STAT3 Transcription Factor; C550182:beta-aminoarteether maleate; D007371:Interferon-gamma; C031327:artemisinin; D000098546:Interleukin-21