Flt3 ligand expands CD103⁺ dendritic cells and FoxP3⁺ T regulatory cells, and attenuates Crohn's-like murine ileitis.
Flt3 ligand expands CD103⁺ dendritic cells and FoxP3⁺ T regulatory cells, and attenuates Crohn's-like murine ileitis.
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DOI：
10.1136/gutjnl-2011-300820
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发表时间：
2012-08
期刊：
影响因子：
24.5
通讯作者：
Rivera-Nieves J
中科院分区：
文献类型：
--
作者：
Collins CB;Aherne CM;McNamee EN;Lebsack MD;Eltzschig H;Jedlicka P;Rivera-Nieves J
Imprinting an effector or regulatory phenotype on naïve T cells requires education at induction sites by dendritic cells (DC). In the current studies we analyzed 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. Using a TNF-driven model of ileitis (i.e. TNFΔARE) that recapitulates many features of Crohn’s disease (CD), we assessed dynamic changes in the frequency and functional state of MP within the inflamed ileum by flow cytometry, immunofluorescence and real-time reverse-transcription polymerase chain reaction and by generating CX3CR1 GFP-reporter TNFΔARE mice. Finally, we assessed the effect of Flt3-L supplementation on the severity of ileitis, the frequency of CD103+ DC and of FoxP3+ Tregs in TNFΔARE mice. 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+ Tregs. Our findings support a role for Flt3-L as a potential therapeutic in Crohn’s-like ileitis.
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