The influence of excessive IL-6 production in vivo on the development and function of Foxp3+ regulatory T cells

Minoru Fujimoto, Mayumi Nakano, Fumitaka Terabe, Hirohisa Kawahata, Tomoharu Ohkawara, Yongmei Han, Barry Ripley, Satoshi Serada, Teppei Nishikawa, Akihiro Kimura, Shintaro Nomura, Tadamitsu Kishimoto, Tetsuji Naka

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105 Citations (Scopus)

Abstract

IL-6 is a proinflammatory cytokine and its overproduction is implicated in a variety of inflammatory disorders. Recent in vitro analyses suggest that IL-6 is a key cytokine that determines the balance between Foxp3+ regulatory T cells (Tregs) and Th17 cells. However, it remains unclear whether excessive IL-6 production in vivo alters the development and function of Foxp3+ Tregs. In this study, we analyzed IL-6 transgenic (Tg) mice in which serum IL-6 levels are constitutively elevated. Interestingly, in IL-6 Tg mice, whereas peripheral lymphoid organs were enlarged, and T cells exhibited activated phenotype, Tregs were not reduced but rather increased compared with wild-type mice. In addition, Tregs from Tg mice normally suppressed proliferation of naive T cells in vitro. Furthermore, Tregs cotransferred with naive CD4 T cells into SCID-IL-6 Tg mice inhibited colitis as successfully as those transferred into control SCID mice. These results indicate that overproduction of IL-6 does not inhibit development or function of Foxp3 + Tregs in vivo. However, when naive CD4 T cells alone were transferred, Foxp3+ Tregs retrieved from SCID-IL-6 Tg mice were reduced compared with SCID mice. Moreover, the Helios- subpopulation of Foxp3+ Tregs, recently defined as extrathymic Tregs, was significantly reduced in IL-6 Tg mice compared with wild-type mice. Collectively, these results suggest that IL-6 overproduced in vivo inhibits inducible Treg generation from naive T cells, but does not affect the development and function of natural Tregs.

Original languageEnglish
Pages (from-to)32-40
Number of pages9
JournalJournal of Immunology
Volume186
Issue number1
DOIs
Publication statusPublished - 2011 Jan 1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Fujimoto, M., Nakano, M., Terabe, F., Kawahata, H., Ohkawara, T., Han, Y., Ripley, B., Serada, S., Nishikawa, T., Kimura, A., Nomura, S., Kishimoto, T., & Naka, T. (2011). The influence of excessive IL-6 production in vivo on the development and function of Foxp3+ regulatory T cells. Journal of Immunology, 186(1), 32-40. https://doi.org/10.4049/jimmunol.0903314