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

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 demons...

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Detalles Bibliográficos
Autores principales: Okamura, Tomohisa, Sumitomo, Shuji, Morita, Kaoru, Iwasaki, Yukiko, Inoue, Mariko, Nakachi, Shinichiro, Komai, Toshihiko, Shoda, Hirofumi, Miyazaki, Jun-ichi, Fujio, Keishi, Yamamoto, Kazuhiko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4346620/
https://www.ncbi.nlm.nih.gov/pubmed/25695838
http://dx.doi.org/10.1038/ncomms7329
Descripción
Sumario: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.

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