Dendritic cell expression of the signaling molecule TRAF6 is critical for gut microbiota-dependent immune tolerance.
Immunity
; 38(6): 1211-22, 2013 Jun 27.
Article
en En
| MEDLINE
| ID: mdl-23791643
ABSTRACT
The intracellular signaling molecule TRAF6 is critical for Toll-like receptor (TLR)-mediated activation of dendritic cells (DCs). We now report that DC-specific deletion of TRAF6 (TRAF6ΔDC) resulted, unexpectedly, in loss of mucosal tolerance, characterized by spontaneous development of T helper 2 (Th2) cells in the lamina propria and eosinophilic enteritis and fibrosis in the small intestine. Loss of tolerance required the presence of gut commensal microbiota but was independent of DC-expressed MyD88. Further, TRAF6ΔDC mice exhibited decreased regulatory T (Treg) cell numbers in the small intestine and diminished induction of iTreg cells in response to model antigen. Evidence suggested that this defect was associated with diminished DC expression of interleukin-2 (IL-2). Finally, we demonstrate that aberrant Th2 cell-associated responses in TRAF6ΔDC mice could be mitigated via restoration of Treg cell activity. Collectively, our findings reveal a role for TRAF6 in directing DC maintenance of intestinal immune tolerance through balanced induction of Treg versus Th2 cell immunity.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Células Dendríticas
/
Linfocitos T Reguladores
/
Células Th2
/
Factor 6 Asociado a Receptor de TNF
/
Enteritis
/
Eosinofilia
/
Eosinófilos
/
Gastritis
/
Intestinos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Immunity
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2013
Tipo del documento:
Article
País de afiliación:
Estados Unidos