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TGF-?3-expressing CD4+CD25(-)LAG3+ regulatory T cells control humoral immune responses.

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-?3 in an Egr2- and Fas-dependent manner. LAG3(+) Treg require TGF-?3 to suppress B-cell responses in a murine model of lupus. Moreover, TGF-?3- and LAG3(+) Treg-mediated suppression requires PD-1 expression on B cells. We also show that TGF-?3-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.

SUBMITTER: Okamura T

PROVIDER: S-EPMC4346620 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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TGF-β3-expressing CD4+CD25(-)LAG3+ regulatory T cells control humoral immune responses.

Okamura Tomohisa T Sumitomo Shuji S Morita Kaoru K Iwasaki Yukiko Y Inoue Mariko M Nakachi Shinichiro S Komai Toshihiko T Shoda Hirofumi H Miyazaki Jun-Ichi J Fujio Keishi K Yamamoto Kazuhiko K

Nature communications 20150219

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 ...[more]

PMID: 25695838

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