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    Flt3 ligand expands CD103+ dendritic cells and FoxP3+ T regulatory cells, and attenuates Crohn’s-like murine ileitis


    Collins, Colm B. and Aherne, Carol M. and McNamee, Eóin N. and Lebsack, Matthew D.P. and Eltzschig, Holger K. and Jedlicka, Paul and Rivera-Nieves, Jesus (2012) Flt3 ligand expands CD103+ dendritic cells and FoxP3+ T regulatory cells, and attenuates Crohn’s-like murine ileitis. Gut, 61 (8). pp. 1154-1162. ISSN 1468-3288

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    Abstract

    Background Imprinting an effector or regulatory phenotype on naı¨ve 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.

    Item Type: Article
    Keywords: Flt3; ligand; expands; CD103+; dendritic cells; FoxP3+; T regulatory cells; Crohn’s; murine ileitis;
    Academic Unit: Faculty of Science and Engineering > Biology
    Item ID: 12595
    Identification Number: https://doi.org/10.1136/gutjnl-2011-300820
    Depositing User: Eoin McNamee
    Date Deposited: 24 Mar 2020 12:39
    Journal or Publication Title: Gut
    Publisher: BMJ Publishing Group
    Refereed: Yes
    URI:

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