Transcription factor early growth response 3 is associated with the TGF-β1 expression and the regulatory activity of CD4-positive T cells in vivo

Shuji Sumitomo, Keishi Fujio, Tomohisa Okamura, Kaoru Morita, Kazuyoshi Ishigaki, Keigo Suzukawa, Kaori Kanaya, Kenji Kondo, Tatsuya Yamasoba, Asayo Furukawa, Noburou Kitahara, Hirofumi Shoda, Mihoko Shibuya, Akiko Okamoto, Kazuhiko Yamamoto

研究成果: Article査読

18 被引用数 (Scopus)

抄録

TGF-β1 is an important anti-inflammatory cytokine, and several regulatory T cell (Treg) subsets including CD4+CD25 +Foxp3+ Tregs and Th3 cells have been reported to exert regulatory activity via the production of TGF-β1. However, it has not yet been elucidated which transcription factor is involved in TGF-β1 transcription. Early growth response 3 (Egr-3) is a zinc-finger transcription factor that creates and maintains T cell anergy. In this study, we found that Egr-3 induces the expression of TGF-β1 in both murine and human CD4 + T cells. Egr-3 overexpression in murine CD4+ T cells induced the production of TGF-β1 and enhanced the phosphorylation of STAT3, which is associated with TGF-β1 transcription. Moreover, Egr-3 conferred Ag-specific regulatory activity on murine CD4+ T cells. In collagen-induced arthritis and delayed-type hypersensitivity model mice, Egr-3-transduced CD4+ T cells exhibited significant regulatory activity in vivo. In particular, the suppression of delayedtype hypersensitivity depended on TGF-β1. In human tonsils, we found that CD4 +CD25-CD45RO-lymphocyte activation gene 3 (LAG3)- T cells express membrane-bound TGF-β1 in an EGR3-dependent manner. Gene-expression analysis revealed that CD4+ CD25-CD45RO-LAG3- T cells are quite different from conventional CD4+CD25+Foxp3+ Tregs. Intriguingly, the CD4+CD25-CD45RO-LAG3 - T cells suppressed graft-versus-host disease in immunodeficient mice transplanted with human PBMCs. Our results suggest that Egr-3 is a transcription factor associated with TGF-β1 expression and in vivo regulatory activity in both mice and humans.

本文言語English
ページ(範囲)2351-2359
ページ数9
ジャーナルJournal of Immunology
191
5
DOI
出版ステータスPublished - 2013 9月 1
外部発表はい

ASJC Scopus subject areas

  • 免疫アレルギー学
  • 免疫学

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