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

J Immunol. 2010 Oct 1;185(7):4223-32. doi: 10.4049/jimmunol.0903507. Epub 2010 Sep 3.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation / immunology
  • Blotting, Western
  • Cancer Vaccines / immunology*
  • Cancer Vaccines / metabolism
  • Cell Proliferation
  • Cell Separation
  • Cell Survival / immunology
  • Chemotaxis, Leukocyte / immunology*
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Interleukin-1 Receptor-Associated Kinases / immunology*
  • Interleukin-1 Receptor-Associated Kinases / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL


  • Cancer Vaccines
  • IRAK3 protein, human
  • Interleukin-1 Receptor-Associated Kinases