Format

Send to

Choose Destination
Nat Commun. 2015 Feb 19;6:6329. doi: 10.1038/ncomms7329.

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

Author information

1
1] Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan [2] Max Planck-The University of Tokyo Center for Integrative Inflammology, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505, Japan.
2
Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
3
Division of Stem Cell Regulation Research, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.

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.

PMID:
25695838
PMCID:
PMC4346620
DOI:
10.1038/ncomms7329
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center