Dendritic cells require the NF-κB2 pathway for cross-presentation of soluble antigens

Evan F. Lind, Cory L. Ahonen, Anna Wasiuk, Yoko Kosaka, Burkhard Becher, Kathy A. Bennett, Randolph J. Noelle

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

NF-κB-inducing kinasc (NIK) is responsible for activation of the non-canonical p100 processing pathway of NF-κB activation. This kinase has been shown to be critical for activation of this pathway after signaling through several TNF family members including CD40. The functional importance of this pathway in CD40 and TLR-induced dendritic cell (DC) differentiation was studied in vivo in the alymphoplasia (Aly) mouse. The Aly mouse expresses a mutant NIK molecule that prohibits the induction of the non-canonical pathway. We show that while MHC class II presentation and in vivo migration of Aly DCs is intact, these cells are unable to cross-prime CD8+ T cells to exogenous Ag. Gene expression array analysis of DCs matured in vivo indicates multiple defects in Ag processing pathways after maturation and provide a global view of the genes that are regulated by the NF-κB2 pathway in DCs. These experiments indicate a possible role for NIK in mediating cross-priming of soluble Ag. In addition, our findings explain the profound immune unresponsiveness of the Aly mouse.

Original languageEnglish (US)
Pages (from-to)354-363
Number of pages10
JournalJournal of Immunology
Volume181
Issue number1
DOIs
StatePublished - 2008

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Lind, E. F., Ahonen, C. L., Wasiuk, A., Kosaka, Y., Becher, B., Bennett, K. A., & Noelle, R. J. (2008). Dendritic cells require the NF-κB2 pathway for cross-presentation of soluble antigens. Journal of Immunology, 181(1), 354-363. https://doi.org/10.4049/jimmunol.181.1.354