Mouse immune thrombocytopenia is associated with Th1 bias and expression of activating Fcγ receptors

• Published in: International journal of hematology 2017-05, Vol.105 (5), p.598-605
• Main Authors: Nishimoto, Tetsuya, Okazaki, Yuka, Numajiri, Miku, Kuwana, Masataka
• Format: Article
• Language: English
• Subjects: Animals; Autoimmunity; Blood Platelets - immunology; Disease Models, Animal; Female; Gene Expression; Hematology; Macrophages - immunology; Medicine; Medicine & Public Health; Mice, Inbred BALB C; Oncology; Original Article; Purpura, Thrombocytopenic, Idiopathic - immunology; Receptors, IgG - genetics; Receptors, IgG - metabolism; T-Lymphocytes, Regulatory; Th1 Cells - immunology
• ISSN: 0925-5710; 1865-3774
• DOI: 10.1007/s12185-016-2172-2

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 IgG 2a and IgG 2b . 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.