Oral interleukin-10 alleviates polyposis via neutralization of pathogenic T-regulatory cells

Allen Y. Chung, Qingsheng Li, Sarah J. Blair, Magdia De Jesus, Kristen L. Dennis, Charles Levea, Jin Yao, Yijun Sun, Thomas F. Conway, Lauren P. Virtuoso, Nicholas G. Battaglia, Stacia Furtado, Edith Mathiowitz, Nicholas J. Mantis, Khashayarsha Khazaie, Nejat K. Egilmez

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

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 multiorgan toxicities. Here, we demonstrate, in a murine model of spontaneous gastrointestinal polyposis, that site-specific uptake of orally administered IL10 microparticles 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+ RoRyt+ IL17+ pathogenic T-regulatory cells (pgTreg), with a concomitant restoration of FoxP3+ RoRyt- 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. Furthermore, they implicate local manipulation of IL10 as a tractable therapeutic strategy to address the inflammatory sequelae associated with mucosal premalignancy.

Original languageEnglish (US)
Pages (from-to)5377-5385
Number of pages9
JournalCancer research
Volume74
Issue number19
DOIs
StatePublished - Oct 1 2014

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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