Absence of IFN-β impairs antigen presentation capacity of splenic dendritic cells via down-regulation of heat shock protein 70

Natalia Ziȩtara*, Marcin Łyszkiewicz, Nelson Gekara, Jacek Puchałka, Vitor A.P. Martins Dos Santos, Clayton R. Hunt, Tej K. Pandita, Stefan Lienenklaus, Siegfried Weiss

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

27 Citations (Scopus)

Abstract

Type I IFNs play a key role in linking the innate and adaptive arms of the immune system. Although produced rapidly in response to pathogens, IFNs are also produced at low levels in the absence of infection. In the present study, we demonstrate that constitutively produced IFNs are necessary in vivo to maintain dendritic cells in an "Ag presentation-competent" state. Conventional dendritic cells (cDCs) isolated from spleens of IFN-β or IFNAR-deficient mice exhibit a highly impaired ability to present Ag and activate naive T cells. Microarray analysis of mRNA isolated from IFN-β-/- and IFNAR-/- cDCs revealed diminished expression of two genes that encoded members of the heat shock protein 70 (Hsp70) family. Consistent with this observation, pharmacological inhibition of Hsp70 in cDCs from wild-type mice impaired their T cell stimulatory capacity. Similarly, the Ag presentation ability of splenic cDCs isolated from Hsp70.1/3-/- mice was also severely impaired in comparison to wild-type cDCs. Thus, constitutive IFN-β expression regulates Hsp70 levels to help maintain dendritic cells in a competent state for efficient priming of effector T cells in vivo.

Original languageEnglish
Pages (from-to)1099-1109
Number of pages11
JournalJournal of Immunology
Volume183
Issue number2
DOIs
Publication statusPublished - 15 Jul 2009
Externally publishedYes

Fingerprint Dive into the research topics of 'Absence of IFN-β impairs antigen presentation capacity of splenic dendritic cells via down-regulation of heat shock protein 70'. Together they form a unique fingerprint.

Cite this