TGF-ß3-expressing CD4+CD25(-)LAG3+ regulatory T cells control humoral immune responses.
Nat Commun
; 6: 6329, 2015 Feb 19.
Article
en En
| MEDLINE
| ID: mdl-25695838
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-ß3 in an Egr2- and Fas-dependent manner. LAG3(+) Treg require TGF-ß3 to suppress B-cell responses in a murine model of lupus. Moreover, TGF-ß3- and LAG3(+) Treg-mediated suppression requires PD-1 expression on B cells. We also show that TGF-ß3-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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Linfocitos T CD4-Positivos
/
Proteína 2 de la Respuesta de Crecimiento Precoz
/
Factor de Crecimiento Transformador beta3
/
Inmunidad Humoral
/
Lupus Eritematoso Sistémico
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Nat Commun
Asunto de la revista:
BIOLOGIA
/
CIENCIA
Año:
2015
Tipo del documento:
Article
País de afiliación:
Japón