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TGF-β3-expressing CD4+CD25−LAG3+ regulatory T cells control humoral immune responses

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  • Tomohisa Okamura

    (Graduate School of Medicine, The University of Tokyo
    Max Planck-The University of Tokyo Center for Integrative Inflammology, The University of Tokyo)

  • Shuji Sumitomo

    (Graduate School of Medicine, The University of Tokyo)

  • Kaoru Morita

    (Graduate School of Medicine, The University of Tokyo)

  • Yukiko Iwasaki

    (Graduate School of Medicine, The University of Tokyo)

  • Mariko Inoue

    (Graduate School of Medicine, The University of Tokyo)

  • Shinichiro Nakachi

    (Graduate School of Medicine, The University of Tokyo)

  • Toshihiko Komai

    (Graduate School of Medicine, The University of Tokyo)

  • Hirofumi Shoda

    (Graduate School of Medicine, The University of Tokyo)

  • Jun-ichi Miyazaki

    (Osaka University Graduate School of Medicine)

  • Keishi Fujio

    (Graduate School of Medicine, The University of Tokyo)

  • Kazuhiko Yamamoto

    (Graduate School of Medicine, The University of Tokyo)

Abstract

Autoantibodies induce various autoimmune diseases, including systemic lupus erythematosus (SLE). We previously described that CD4+CD25−LAG3+ regulatory T cells (LAG3+ Treg) are regulated by Egr2, a zinc-finger transcription factor required for the induction of T-cell anergy. We herein demonstrate that LAG3+ Treg produce high amounts of TGF-β3 in an Egr2- and Fas-dependent manner. LAG3+ Treg require TGF-β3 to suppress B-cell responses in a murine model of lupus. Moreover, TGF-β3- and LAG3+ Treg-mediated suppression requires PD-1 expression on B cells. We also show that TGF-β3-expressing human LAG3+ Treg suppress antibody production and that SLE patients exhibit decreased frequencies of LAG3+ Treg. These results clarify the mechanism of B-cell regulation and suggest therapeutic strategies.

Suggested Citation

  • Tomohisa Okamura & Shuji Sumitomo & Kaoru Morita & Yukiko Iwasaki & Mariko Inoue & Shinichiro Nakachi & Toshihiko Komai & Hirofumi Shoda & Jun-ichi Miyazaki & Keishi Fujio & Kazuhiko Yamamoto, 2015. "TGF-β3-expressing CD4+CD25−LAG3+ regulatory T cells control humoral immune responses," Nature Communications, Nature, vol. 6(1), pages 1-14, May.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7329
    DOI: 10.1038/ncomms7329
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    Cited by:

    1. Jun Inamo & Akari Suzuki & Mahoko Takahashi Ueda & Kensuke Yamaguchi & Hiroshi Nishida & Katsuya Suzuki & Yuko Kaneko & Tsutomu Takeuchi & Hiroaki Hatano & Kazuyoshi Ishigaki & Yasushi Ishihama & Kazu, 2024. "Long-read sequencing for 29 immune cell subsets reveals disease-linked isoforms," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

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