| Literature DB >> 25695838 |
Tomohisa Okamura1, Shuji Sumitomo2, Kaoru Morita2, Yukiko Iwasaki2, Mariko Inoue2, Shinichiro Nakachi2, Toshihiko Komai2, Hirofumi Shoda2, Jun-Ichi Miyazaki3, Keishi Fujio2, Kazuhiko Yamamoto2.
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.Entities:
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Year: 2015 PMID： 25695838 PMCID： PMC4346620 DOI： 10.1038/ncomms7329
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919