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

Tomohisa Okamura, Shuji Sumitomo, Kaoru Morita, Yukiko Iwasaki, Mariko Inoue, Shinichiro Nakachi, Toshihiko Komai, Hirofumi Shoda, Jun-ichi Miyazaki, Keishi Fujio () and Kazuhiko Yamamoto
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Tomohisa Okamura: Graduate School of Medicine, 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

Nature Communications, 2015, vol. 6, issue 1, 1-14

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms7329

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