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Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Cancer+Res 2014 ; 74 (19): 5377-85 Nephropedia Template TP
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Oral interleukin-10 alleviates polyposis via neutralization of pathogenic T-regulatory cells #MMPMID25228656
Chung AY; Li Q; Blair SJ; De Jesus M; Dennis KL; LeVea C; Yao J; Sun Y; Conway TF; Virtuoso LP; Battaglia NG; Furtado S; Mathiowitz E; Mantis NJ; Khazaie K; Egilmez NK
Cancer Res 2014[Oct]; 74 (19): 5377-85 PMID25228656show ga
Immune dysregulation drives the pathogenesis of chronic inflammatory, autoimmune and dysplastic disorders. While often intended to address localized pathology, most immune modulatory therapies are administered systemically and carry inherent risk of multi-organ toxicities. Here we demonstrate, in a murine model of spontaneous gastrointestinal polyposis, that site-specific uptake of orally-administered microparticles of the interleukin IL-10 ameliorates local and systemic disease to enhance survival. Mechanistic investigations showed that the therapeutic benefit of this treatment derived from neutralization of disease-promoting FoxP3+RoR?t+IL17+ pathogenic T-regulatory cells (pgTreg), with a concomitant restoration of FoxP3+RoR?t-IL17- conventional T regulatory cells (Treg). These findings provide a proof-of-principle for the ability of an oral biologic to restore immune homeostasis at the intestinal surface. Further, they implicate local manipulation of IL-10 as a tractable therapeutic strategy to address the inflammatory sequelae associated with mucosal premalignancy.