title: Mouse immune thrombocytopenia is associated with Th1 bias and expression of activating Fcγ receptors.
abstract: Immune thrombocytopenia (ITP) is an autoimmune disease mediated by anti-platelet autoantibodies. We recently established a mouse ITP model exhibiting regulatory T-cell (Treg) deficiency, although only one-third of the Treg-deficient mice developed ITP. To clarify mechanisms involved in the emergence of platelet-specific autoimmunity in this model, we examined the T helper (Th)-cell balance and macrophage Fcγ receptor (FcγR) expression profiles in Treg-deficient mice with and without ITP. Splenocytes from both populations of Treg-deficient mice and control BALB/c mice were subjected to flow cytometry-based analyses to evaluate Th cell subset proportions and the expression of activating and inhibitory FcγRs on macrophages. In addition, IgG subclass distribution of anti-platelet autoantibodies in splenocyte culture supernatants was determined by flow cytometry using IgG subclass-specific antibodies. Treg-deficient ITP mice exhibited a significantly higher proportion of Th1 cells than either Treg-deficient non-ITP or control mice. The predominant anti-platelet autoantibody subclasses in the ITP mice were Th1-associated IgG2aand IgG2b. Furthermore, the FcγRI/FcγRIIB expression ratio in splenic macrophages was higher in the Treg-deficient ITP than in the Treg-deficient non-ITP and control mice. In summary, Th1 polarization and macrophages' activating FcγR expression profile are associated with the development of ITP in Treg-deficient mice.
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.affiliation: Department of Allergy and Rheumatology, Nippon Medical School Graduate School of Medicine, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Okazaki
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
authors.forename: Miku
authors.initials: M
authors.lastname: Numajiri
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. kuwanam@nms.ac.jp.|Department of Allergy and Rheumatology, Nippon Medical School Graduate School of Medicine, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan. kuwanam@nms.ac.jp.
authors.forename: Masataka
authors.identifier: http://orcid.org/0000-0001-8352-6136
authors.initials: M
authors.lastname: Kuwana
mesh_terms: D000818:Animals; D015551:Autoimmunity; D001792:Blood Platelets / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D008264:Macrophages / Q000276:immunology; D008807:Mice, Inbred BALB C; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000276:immunology*; D017452:Receptors, IgG / Q000235:genetics / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory; D018417:Th1 Cells / Q000276:immunology*
chemical_list: C485701:Fcgr1 protein, mouse; C499172:Fcgr2b protein, mouse; D017452:Receptors, IgG
keywords: Autoantibody; Fc receptors; Immune thrombocytopenia; Regulatory T cells; T helper cells