title: Overexpression of RORγt under control of the CD2 promoter induces polyclonal plasmacytosis and autoantibody production in transgenic mice.
abstract: Retinoic acid related orphan receptor gamma-t (RORγt) is known to be a master regulator of Th17-cell development. In this study, we generated RORγt-overexpressing transgenic (RORγt Tg) mice in which transgene expression was driven by the CD2 promoter, and found that these mice developed polyclonal plasmacytosis and autoantibody production. RORγt Tg mice were generated on a C57BL/6 background, and also were intercrossed with BALB/c mice. BALB/c F1 (BALB/F1) RORγt 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 RORγt Tg mice. In the present study, polyclonal plasmacytosis in BALB/F1 RORγt 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 RORγt 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 RORγt Tg mice, might effect the development of plasma-cytosis. These results suggest that RORγt plays important roles in the development of plasmacytosis and autoantibody production.
authors.affiliation: Department of Nephrology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan. k-yohnpr@umin.ac.jp
authors.forename: Keigyou
authors.initials: K
authors.lastname: Yoh
authors.forename: Naoki
authors.initials: N
authors.lastname: Morito
authors.forename: Masami
authors.initials: M
authors.lastname: Ojima
authors.forename: Kazuko
authors.initials: K
authors.lastname: Shibuya
authors.forename: Yumi
authors.initials: Y
authors.lastname: Yamashita
authors.forename: Yuko
authors.initials: Y
authors.lastname: Morishima
authors.forename: Yukio
authors.initials: Y
authors.lastname: Ishii
authors.forename: Manabu
authors.initials: M
authors.lastname: Kusakabe
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Nishikii
authors.forename: Akiko
authors.initials: A
authors.lastname: Fujita
authors.forename: Emi
authors.initials: E
authors.lastname: Matsunaga
authors.forename: Midori
authors.initials: M
authors.lastname: Okamura
authors.forename: Michito
authors.initials: M
authors.lastname: Hamada
authors.forename: Akira
authors.initials: A
authors.lastname: Suto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakajima
authors.forename: Akira
authors.initials: A
authors.lastname: Shibuya
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Yamagata
authors.forename: Satoru
authors.initials: S
authors.lastname: Takahashi
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis*; D001792:Blood Platelets / Q000276:immunology; D039481:CD11b Antigen / Q000096:biosynthesis; D018801:CD2 Antigens / Q000235:genetics; D004247:DNA / Q000276:immunology; D004912:Erythrocytes / Q000276:immunology; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000097:blood / Q000378:metabolism; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D008168:Lung / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000378:metabolism*; D010950:Plasma Cells / Q000502:physiology*; D011401:Promoter Regions, Genetic; D011694:Purpura, Hyperglobulinemic / Q000276:immunology; D013163:Splenomegaly / Q000276:immunology
chemical_list: D001323:Autoantibodies; D039481:CD11b Antigen; D018801:CD2 Antigens; D020381:Interleukin-17; D015850:Interleukin-6; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D004247:DNA