| First Author | Okamura T | Year | 2015 |
| Journal | Nat Commun | Volume | 6 |
| Pages | 6329 | PubMed ID | 25695838 |
| Mgi Jnum | J:221793 | Mgi Id | MGI:5641571 |
| Doi | 10.1038/ncomms7329 | Citation | Okamura T, et al. (2015) TGF-beta3-expressing CD4+CD25(-)LAG3+ regulatory T cells control humoral immune responses. Nat Commun 6:6329 |
| abstractText | 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-beta3 in an Egr2- and Fas-dependent manner. LAG3(+) Treg require TGF-beta3 to suppress B-cell responses in a murine model of lupus. Moreover, TGF-beta3- and LAG3(+) Treg-mediated suppression requires PD-1 expression on B cells. We also show that TGF-beta3-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. |
