title: Induction of immune tolerance to platelet antigen by short-term thrombopoietin treatment in a mouse model of immune thrombocytopenia.
abstract: Immune thrombocytopenia (ITP) is an autoimmune disorder caused by IgG anti-platelet autoantibodies. Thrombopoietin (TPO) receptor agonists are highly effective in inducing the recovery of platelet counts in ITP patients. Although these agents are thought to promote platelet production without affecting the autoimmune pathogenesis of the disease, a small subset of ITP patients exhibits sustained platelet recovery after treatment termination. To investigate mechanisms involved in this sustained recovery, we evaluated the effects of short-term TPO treatment using a mouse ITP model generated by Foxp3(+) T regulatory cell (Treg) depletion. After treatment, platelet recovery was sustained, along with complete suppression of both anti-platelet autoantibody production and T-cell responses to platelet autoantigens. TPO treatment also promoted the peripheral induction of Foxp3(+) Tregs in conjunction with elevated circulating TGF-β levels. In summary, thrombopoietic agents are capable of inducing immune tolerance to platelet autoantigens, thereby suppressing the autoimmune pathogenesis of ITP.
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Nishimoto
authors.forename: Miku
authors.initials: M
authors.lastname: Numajiri
authors.forename: Hisataka
authors.initials: H
authors.lastname: Nakazaki
authors.forename: Yuka
authors.initials: Y
authors.lastname: Okazaki
authors.forename: Masataka
authors.initials: M
authors.lastname: Kuwana
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D001792:Blood Platelets / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D007108:Immune Tolerance / Q000187:drug effects*; D007519:Isoantigens / Q000276:immunology*; D051379:Mice; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology; D013926:Thrombopoietin / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000276:immunology
chemical_list: D001323:Autoantibodies; D007519:Isoantigens; D016212:Transforming Growth Factor beta; D013926:Thrombopoietin