期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 42, 期 8, 页码 1999-2009出版社
WILEY
DOI: 10.1002/eji.201142250
关键词
Autoantibody; Plasmacytosis; ROR?t; Th17; Thrombocytopenia
类别
资金
- Ministry of Education, Science, Sports and Culture, Japan
- Japanese Ministry of Health, Labour and Welfare
- Grants-in-Aid for Scientific Research [22390073, 23591432, 24591223, 24659176, 22590876] Funding Source: KAKEN
Retinoic acid related orphan receptor gamma-t (ROR?t) is known to be a master regulator of Th17-cell development. In this study, we generated ROR?t-overexpressing transgenic (ROR?t Tg) mice in which transgene expression was driven by the CD2 promoter, and found that these mice developed polyclonal plasmacytosis and autoantibody production. ROR?t Tg mice were generated on a C57BL/6 background, and also were intercrossed with BALB/c mice. BALB/c F1 (BALB/F1) ROR?t Tg mice developed massive polyclonal plasma-cytosis, and had shorter life spans. Splenomegaly and infiltration of plasma cells into the lung were observed. Hyperglobulinemia, anti-double-stranded DNA antibodies, anti-erythrocyte antibodies, and anti-platelet antibodies were detected in BALB/F1 ROR?t Tg mice. In the present study, polyclonal plasmacytosis in BALB/F1 ROR?t Tg mice appeared to be due to the induction of excessive IL-6 production by IL-17. We detected increased numbers of CD11b+ cells that produced IL-6. We also generatedIL-6-deficient ROR?t Tg BALB/F1 background mice, which displayed high levels of serum IL-17, but did not develop severe hyperglobulinemia. Excessive IL-6 production by several cell types, including macrophages, in BALB/F1 ROR?t Tg mice, might effect the development of plasma-cytosis. These results suggest that ROR?t plays important roles in the development of plasmacytosis and autoantibody production.
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