論文 - 詳細
| RRC ID | 87943 |
|---|---|
| 著者 | Okamura T, Sumitomo S, Morita K, Iwasaki Y, Inoue M, Nakachi S, Komai T, Shoda H, Miyazaki J, Fujio K, Yamamoto K. |
| タイトル | TGF-β3-expressing CD4+CD25(-)LAG3+ regulatory T cells control humoral immune responses. |
| ジャーナル | Nat Commun |
| 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. |
| 巻・号 | 6 |
| ページ | 6329 |
| 公開日 | 2015-2-19 |
| DOI | 10.1038/ncomms7329 |
| PII | ncomms7329 |
| PMID | 25695838 |
| PMC | PMC4346620 |
| MeSH | Animals Antigens, CD / metabolism B-Lymphocytes / cytology CD4-Positive T-Lymphocytes / cytology* Disease Models, Animal Early Growth Response Protein 2 / metabolism* Female Humans Immunity, Humoral / immunology* Interleukin-2 Receptor alpha Subunit / metabolism Lupus Erythematosus, Systemic / metabolism* Lymphocyte Activation Gene 3 Protein Male Mice Mice, Inbred C57BL Mice, Knockout Spleen / metabolism T-Lymphocytes, Regulatory / cytology Transforming Growth Factor beta3 / metabolism* |
| IF | 12.121 |
| リソース情報 | |
| 実験動物マウス | RBRC02142 |