Overexpression of ROR γt under control of the CD 2 promoter induces polyclonal plasmacytosis and autoantibody production in transgenic mice

Retinoic acid related orphan receptor gamma‐t ( ROR γt) is known to be a master regulator of T h17‐cell development. In this study, we generated ROR γt‐overexpressing transgenic ( ROR γt T g) mice in which transgene expression was driven by the CD 2 promoter, and found that these mice developed poly...

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Published in:European journal of immunology 2012-08, Vol.42 (8), p.1999-2009
Main Authors: Yoh, Keigyou, Morito, Naoki, Ojima, Masami, Shibuya, Kazuko, Yamashita, Yumi, Morishima, Yuko, Ishii, Yukio, Kusakabe, Manabu, Nishikii, Hidekazu, Fujita, Akiko, Matsunaga, Emi, Okamura, Midori, Hamada, Michito, Suto, Akira, Nakajima, Hiroshi, Shibuya, Akira, Yamagata, Kunihiro, Takahashi, Satoru
Format: Article
Language:English
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Summary:Retinoic acid related orphan receptor gamma‐t ( ROR γt) is known to be a master regulator of T h17‐cell development. In this study, we generated ROR γt‐overexpressing transgenic ( ROR γt T g) mice in which transgene expression was driven by the CD 2 promoter, and found that these mice developed polyclonal plasmacytosis and autoantibody production. ROR γt T g mice were generated on a C 57 BL /6 background, and also were intercrossed with B ALB/c mice. B ALB/c F 1 ( B ALB/ F 1) ROR γt T g 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 B ALB/ F 1 ROR γt T g mice. In the present study, polyclonal plasmacytosis in B ALB/ F 1 ROR γt T g mice appeared to be due to the induction of excessive IL ‐6 production by IL ‐17. We detected increased numbers of CD 11b + cells that produced IL ‐6. We also generated IL ‐6‐deficient ROR γt T g B ALB/ F 1 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 B ALB/ F 1 ROR γt T g mice, might effect the development of plasma‐cytosis. These results suggest that ROR γt plays important roles in the development of plasmacytosis and autoantibody production.
ISSN:0014-2980
1521-4141
DOI:10.1002/eji.201142250