Type I interferons maintain Foxp3 expression and T-regulatory cell functions under inflammatory conditions in mice.
Gastroenterology
; 143(1): 145-54, 2012 Jul.
Article
em En
| MEDLINE
| ID: mdl-22475534
ABSTRACT
BACKGROUND & AIMS:
Foxp3(+) T-regulatory cells (Tregs) maintain intestinal homeostasis under conditions of continuous challenge with inflammatory microbes. However, plasticity of the Treg population under certain conditions has been reported; Foxp3(+) Tregs can be converted to Foxp3(-) CD4(+) T cells.METHODS:
We used mice with a T cell-induced colitis model to study the regulatory role of type I interferons (IFNs) in adaptive immunity. We transferred CD4(+)CD45RB(hi) (RB(hi)) T cells, with or without CD4(+)CD45RB(lo) CD25(+) T cells, from wild-type or IFN-αßR(-/-) mice into Rag1(-/-) recipients. We analyzed induction of colitis by flow cytometry, confocal microscopy, and enzyme-linked immunosorbent assay and reverse-transcription polymerase chain reaction analyses. IFN-αßR(-/-)Rag(-/-) mice were given injections of recombinant IFN-α following transfer of IFN-αßR(-/-) RB(hi) T cells and CD4(+)Foxp3(+) cells from Foxp3-eGFP mice.RESULTS:
Signaling by type I IFNs was required for maintenance of Foxp3 expression and the suppressive activity of Tregs in mice. Transfer of CD4(+)CD45RB(lo)CD25(+) Tregs from IFN-αßR(-/-) mice did not prevent T-cell induction of colitis in mice. Foxp3 expression by Tregs transferred from IFN-αßR(-/-) mice was significantly lower than that of Tregs from wild-type mice. Administration of recombinant IFN-α reduced T cell-mediated colitis by increasing the number of Foxp3(+) Tregs and their suppressive functions.CONCLUSIONS:
Type I IFNs regulate intestinal homeostasis by maintaining Foxp3 expression on Tregs in colons of mice under inflammatory conditions.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article