RT Journal Article
SR Electronic
T1 Flt3 ligand expands CD103<sup>+</sup> dendritic cells and FoxP3<sup>+</sup> T regulatory cells, and attenuates Crohn's-like murine ileitis
JF Gut
JO Gut
FD BMJ Publishing Group Ltd and British Society of Gastroenterology
SP 1154
OP 1162
DO 10.1136/gutjnl-2011-300820
VO 61
IS 8
A1 Colm B Collins
A1 Carol M Aherne
A1 Eóin N McNamee
A1 Matthew D P Lebsack
A1 Holger Eltzschig
A1 Paul Jedlicka
A1 Jesús Rivera-Nieves
YR 2012
UL http://gut.bmj.com/content/61/8/1154.abstract
AB Background Imprinting an effector or regulatory phenotype on naïve T cells requires education at induction sites by dendritic cells (DC).Objectives To analyse the effect of inflammation on the frequency of mononuclear phagocytes (MP) and the effect of altering their frequency by administration of Flt3-L in chronic ileitis.Methods Using a tumour necrosis factor (TNF) driven model of ileitis (ie, TNFΔARE) that recapitulates many features of Crohn's disease (CD), dynamic changes in the frequency and functional state of MP within the inflamed ileum were assessed by flow cytometry, immunofluorescence and real-time reverse-transcription PCR and by generating CX3CR1 GFP-reporter TNFΔARE mice. The effect of Flt3-L supplementation on the severity of ileitis, and the frequency of CD103+ DC and of FoxP3+ regulatory T cells was also studied in TNFΔARE mice.Results CD11cHi/MHCII+ MP accumulated in inflamed ilea, predominantly mediated by expansion of the CX3CR1+ MP subpopulation. This coincided with a decreased pro-regulatory CD103+ DC. The phenotype of these MP was that of activated cells, as they expressed increased CD80 and CD86 on their surface. Flt3-ligand administration resulted in a preferential expansion of CD103+ DC that attenuated the severity of ileitis in 20-week-old TNFΔARE mice, mediated by increased CD4+/CD25+/FoxP3+ regulatory T cells.Conclusions Results support a role for Flt3-L as a potential therapeutic agent in Crohn's-like ileitis.