Back to Search
Start Over
Negative Regulation of IKK ε -Mediated IRF7 Phosphorylation by HSP70.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2020 May 01; Vol. 204 (9), pp. 2562-2574. Date of Electronic Publication: 2020 Mar 13. - Publication Year :
- 2020
-
Abstract
- Immune reactions are controlled by the delicate spatiotemporal orchestration of multiple cells communicating by cytokines. Studies of cytokines that began with the discovery of IFN focused on positive regulatory mechanisms that induce secretion in response to harmful stimuli. However, there is a growing awareness that negative regulatory mechanisms that stop secretion of cytokines at specific times and spaces are also important for a successful immune reaction. Type I IFN is the primary cytokine in innate immunity. Although its induction is a prerequisite for the consequent adaptive immune reaction, its oversecretion can cause destructive tissue damage. IFN regulatory factor 7 (IRF7) is a master transcription factor of type I IFN, and multiple observations indicate the key role of IRF7 and the importance of its negative regulation. In this study, we found that the inducible heat shock protein 70 (HSP70) regulated the early type I IFN response by using mice knockout for HSP70. HSP70 dampened IRF7 activation; the inhibitory effect of HSP70 over IKKε-mediated IRF7 activation originated from simple competitive binding. This suggests the possibility of blocking the feed-forward loop between IRF7 and type I IFN in stress environments with increased expression of HSP70.<br /> (Copyright © 2020 by The American Association of Immunologists, Inc.)
- Subjects :
- Adaptive Immunity genetics
Animals
Female
Immunity, Innate genetics
Interferon Type I genetics
Mice
Mice, Inbred C57BL
Mice, Knockout
Gene Expression Regulation genetics
HSP70 Heat-Shock Proteins genetics
I-kappa B Kinase genetics
Interferon Regulatory Factor-7 genetics
Phosphorylation genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 204
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 32169844
- Full Text :
- https://doi.org/10.4049/jimmunol.1900297