Fueyo-Gonzalez, Francisco, McGinty, Mitchell, Ningoo, Mehek ORCID: 0000-0001-8318-3508, Anderson, Lisa, Cantarelli, Chiara, Angeletti, Andrea, Demir, Markus, Llaudo, Ines, Purroy, Carolina, Marjanovic, Nada, Heja, David, Sealfon, Stuart C., Heeger, Peter S., Cravedi, Paolo and Fribourg, Miguel (2022). Interferon-beta acts directly on T cells to prolong allograft survival by enhancing regulatory T cell induction through Foxp3 acetylation. Immunity, 55 (3). S. 459 - 483. CAMBRIDGE: CELL PRESS. ISSN 1097-4180

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Abstract

Type I interferons (IFNs) are pleiotropic cytokines with potent antiviral properties that also promote protective T cell and humoral immunity. Paradoxically, type I IFNs, including the widely expressed IFN beta, also have immunosuppressive properties, including promoting persistent viral infections and treating T-cell-driven, remitting-relapsing multiple sclerosis. Although associative evidence suggests that IFN beta mediates these immunosuppressive effects by impacting regulatory T (Treg) cells, mechanistic links remain elusive. Here, we found that IFN beta enhanced graft survival in a Treg-cell-dependent murine transplant model. Genetic conditional deletion models revealed that the extended allograft survival was Treg cell-mediated and required IFN beta signaling on T cells. Using an in silico computational model and analysis of human immune cells, we found that IFN beta directly promoted Treg cell induction via STAT1- and P300-dependent Foxp3 acetylation. These findings identify a mechanistic connection between the immunosuppressive effects of IFN beta and Treg cells, with therapeutic implications for transplantation, autoimmunity, and malignancy.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Fueyo-Gonzalez, FranciscoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
McGinty, MitchellUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ningoo, MehekUNSPECIFIEDorcid.org/0000-0001-8318-3508UNSPECIFIED
Anderson, LisaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cantarelli, ChiaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Angeletti, AndreaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Demir, MarkusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Llaudo, InesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Purroy, CarolinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Marjanovic, NadaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heja, DavidUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sealfon, Stuart C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heeger, Peter S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cravedi, PaoloUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fribourg, MiguelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-684877
DOI: 10.1016/j.immuni.2022.01.011
Journal or Publication Title: Immunity
Volume: 55
Number: 3
Page Range: S. 459 - 483
Date: 2022
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 1097-4180
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
INDUCIBLE GENE-EXPRESSION; CHRONIC HEPATITIS-C; I INTERFERON; MULTIPLE-SCLEROSIS; DENDRITIC CELLS; CUTTING EDGE; TARGET GENES; NK CELLS; REJECTION; RESPONSESMultiple languages
ImmunologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/68487

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