IRAK-M removal counteracts dendritic cell vaccine deficits in migration and longevity

Meghan E. Turnis, Xiao Tong Song, Adham Bear, Aaron E. Foster, Stephen Gottschalk, Malcolm Brenner, Si Yi Chen, Cliona M. Rooney

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

To function optimally as vaccines, dendritic cells (DCs) must actively migrate to lymphoid organs and maintain a viable, mature state for sufficient time to effectively present their Ag to cognate T cells. Unfortunately, mature DCs rapidly lose viability and function after injection, and only a minority leaves the vaccine site and migrates to lymph nodes. We show that all of these functions can be enhanced in DCs by removal of IL-1R-associated kinase M (IRAK-M). We found that IRAK-M is induced in DCs by TLR ligation and that its absence from these cells leads to increased activation of the p38-MAPK and NF-κB pathways, which, in turn, improves DC migration to lymph nodes, increases their longevity, and augments their secretion of Th1-skewing cytokines and chemokines. These biological effects have immunological consequences. IRAK-M-/- DCs increase the proliferation and activation of Ag-specific T cells, and a single vaccination with Ag-pulsed, LPS-matured IRAK-M-/- DCs eliminates established tumors and prolongs the survival of EG7 or B16.f10 tumor-bearing mice, without discernible induction of autoimmune disease. Thus, manipulation of IRAK-M levels can increase the potency of DC vaccines by enhancing their Ag-presenting function, migration, and longevity. Copyright

Original languageEnglish (US)
Pages (from-to)4223-4232
Number of pages10
JournalJournal of Immunology
Volume185
Issue number7
DOIs
StatePublished - Oct 1 2010

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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