| First Author | Turnis ME | Year | 2010 |
| Journal | J Immunol | Volume | 185 |
| Issue | 7 | Pages | 4223-32 |
| PubMed ID | 20817880 | Mgi Jnum | J:164297 |
| Mgi Id | MGI:4831068 | Doi | 10.4049/jimmunol.0903507 |
| Citation | Turnis ME, et al. (2010) IRAK-M removal counteracts dendritic cell vaccine deficits in migration and longevity. J Immunol 185(7):4223-32 |
| abstractText | 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-kappaB 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. |
