title: Absence of IFN-beta impairs antigen presentation capacity of splenic dendritic cells via down-regulation of heat shock protein 70.
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-beta or IFNAR-deficient mice exhibit a highly impaired ability to present Ag and activate naive T cells. Microarray analysis of mRNA isolated from IFN-beta(-/-) 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-beta expression regulates Hsp70 levels to help maintain dendritic cells in a competent state for efficient priming of effector T cells in vivo.
authors: Department of Molecular Biotechnology, Molecular Immunology Group, Helmholtz Centre for Infection Research, HZI, Braunschweig, Germany. naz06@helmholtz-hzi.de
authors: Natalia
authors: N
authors: Zietara
authors: Marcin
authors: M
authors: Łyszkiewicz
authors: Nelson
authors: N
authors: Gekara
authors: Jacek
authors: J
authors: Puchałka
authors: Vitor A P Martins
authors: VA
authors: Dos Santos
authors: Clayton R
authors: CR
authors: Hunt
authors: Tej K
authors: TK
authors: Pandita
authors: Stefan
authors: S
authors: Lienenklaus
authors: Siegfried
authors: S
authors: Weiss
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D003713:Dendritic Cells / Q000276:immunology*; D015536:Down-Regulation; D018840:HSP70 Heat-Shock Proteins; D007155:Immunologic Factors; D016899:Interferon-beta / Q000172:deficiency / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D053633:Receptor, Interferon alpha-beta / Q000172:deficiency; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D018840:HSP70 Heat-Shock Proteins; C508032:Ifnar1 protein, mouse; D007155:Immunologic Factors; D053633:Receptor, Interferon alpha-beta; D016899:Interferon-beta