TY - JOUR
T1 - Absence of IFN-β impairs antigen presentation capacity of splenic dendritic cells via down-regulation of heat shock protein 70
AU - Ziȩtara, Natalia
AU - Łyszkiewicz, Marcin
AU - Gekara, Nelson
AU - Puchałka, Jacek
AU - Martins Dos Santos, Vitor A.P.
AU - Hunt, Clayton R.
AU - Pandita, Tej K.
AU - Lienenklaus, Stefan
AU - Weiss, Siegfried
N1 - Copyright:
Copyright 2010 Elsevier B.V., All rights reserved.
PY - 2009/7/15
Y1 - 2009/7/15
N2 - 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.
AB - 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.
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U2 - 10.4049/jimmunol.0803214
DO - 10.4049/jimmunol.0803214
M3 - Article
C2 - 19581626
AN - SCOPUS:70249114855
VL - 183
SP - 1099
EP - 1109
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 2
ER -