Interferon-epsilon is a novel regulator of NK cell responses in the uterus.

Mayall, JR; Horvat, JC; Mangan, NE; Chevalier, A; McCarthy, H; Hampsey, D; Donovan, C; Brown, AC; Matthews, AY; de Weerd, NA; de Geus, ED; Starkey, MR; Kim, RY; Daly, K; Goggins, BJ; Keely, S; Maltby, S; Baldwin, R; Foster, PS; Boyle, MJ; Tanwar, PS; Huntington, ND; Hertzog, PJ; Hansbro, PM

Interferon-epsilon is a novel regulator of NK cell responses in the uterus.

Mayall, JR Horvat, JC Mangan, NE Chevalier, A McCarthy, H Hampsey, D Donovan, C

Brown, AC Matthews, AY de Weerd, NA de Geus, ED Starkey, MR Kim, RY Daly, K Goggins, BJ Keely, S Maltby, S Baldwin, R Foster, PS Boyle, MJ Tanwar, PS Huntington, ND Hertzog, PJ Hansbro, PM

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Publisher:: SPRINGERNATURE
Publication Type:: Journal Article
Citation:: EMBO Mol Med, 2024, 16, (2), pp. 267-293
Issue Date:: 2024-02

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Field	Value	Language
dc.contributor.author	Mayall, JR
dc.contributor.author	Horvat, JC
dc.contributor.author	Mangan, NE
dc.contributor.author	Chevalier, A
dc.contributor.author	McCarthy, H
dc.contributor.author	Hampsey, D
dc.contributor.author	Donovan, C https://orcid.org/0000-0003-4558-329X
dc.contributor.author	Brown, AC
dc.contributor.author	Matthews, AY
dc.contributor.author	de Weerd, NA
dc.contributor.author	de Geus, ED
dc.contributor.author	Starkey, MR
dc.contributor.author	Kim, RY
dc.contributor.author	Daly, K
dc.contributor.author	Goggins, BJ
dc.contributor.author	Keely, S
dc.contributor.author	Maltby, S
dc.contributor.author	Baldwin, R
dc.contributor.author	Foster, PS
dc.contributor.author	Boyle, MJ
dc.contributor.author	Tanwar, PS
dc.contributor.author	Huntington, ND
dc.contributor.author	Hertzog, PJ
dc.contributor.author	Hansbro, PM
dc.date.accessioned	2024-08-01T03:31:19Z
dc.date.available	2023-12-13
dc.date.available	2024-08-01T03:31:19Z
dc.date.issued	2024-02
dc.identifier.citation	EMBO Mol Med, 2024, 16, (2), pp. 267-293
dc.identifier.issn	1757-4676
dc.identifier.issn	1757-4684
dc.identifier.uri	http://hdl.handle.net/10453/179902
dc.description.abstract	The uterus is a unique mucosal site where immune responses are balanced to be permissive of a fetus, yet protective against infections. Regulation of natural killer (NK) cell responses in the uterus during infection is critical, yet no studies have identified uterine-specific factors that control NK cell responses in this immune-privileged site. We show that the constitutive expression of IFNε in the uterus plays a crucial role in promoting the accumulation, activation, and IFNγ production of NK cells in uterine tissue during Chlamydia infection. Uterine epithelial IFNε primes NK cell responses indirectly by increasing IL-15 production by local immune cells and directly by promoting the accumulation of a pre-pro-like NK cell progenitor population and activation of NK cells in the uterus. These findings demonstrate the unique features of this uterine-specific type I IFN and the mechanisms that underpin its major role in orchestrating innate immune cell protection against uterine infection.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	SPRINGERNATURE
dc.relation	http://purl.org/au-research/grants/nhmrc/GNT1079187
dc.relation	http://purl.org/au-research/grants/nhmrc/1059242
dc.relation	http://purl.org/au-research/grants/nhmrc/1003591
dc.relation	http://purl.org/au-research/grants/nhmrc/1175134
dc.relation	http://purl.org/au-research/grants/nhmrc/1079187
dc.relation.ispartof	EMBO Mol Med
dc.relation.isbasedon	10.1038/s44321-023-00018-6
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	06 Biological Sciences, 11 Medical and Health Sciences
dc.subject.classification	3101 Biochemistry and cell biology
dc.subject.mesh	Female
dc.subject.mesh	Humans
dc.subject.mesh	Killer Cells, Natural
dc.subject.mesh	Uterus
dc.subject.mesh	Fetus
dc.subject.mesh	Interferons
dc.subject.mesh	Uterus
dc.subject.mesh	Killer Cells, Natural
dc.subject.mesh	Fetus
dc.subject.mesh	Humans
dc.subject.mesh	Interferons
dc.subject.mesh	Female
dc.subject.mesh	Female
dc.subject.mesh	Humans
dc.subject.mesh	Killer Cells, Natural
dc.subject.mesh	Uterus
dc.subject.mesh	Fetus
dc.subject.mesh	Interferons
dc.title	Interferon-epsilon is a novel regulator of NK cell responses in the uterus.
dc.type	Journal Article
utslib.citation.volume	16
utslib.location.activity	Germany
utslib.for	06 Biological Sciences
utslib.for	11 Medical and Health Sciences
pubs.organisational-group	University of Technology Sydney
pubs.organisational-group	University of Technology Sydney/Faculty of Science
pubs.organisational-group	University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	University of Technology Sydney/Strength - CFI - Centre for Inflammation
utslib.copyright.status	open_access	*
dc.rights.license	This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/
dc.date.updated	2024-08-01T03:31:08Z
pubs.issue	2
pubs.publication-status	Published
pubs.volume	16
utslib.citation.issue	2

Abstract:

The uterus is a unique mucosal site where immune responses are balanced to be permissive of a fetus, yet protective against infections. Regulation of natural killer (NK) cell responses in the uterus during infection is critical, yet no studies have identified uterine-specific factors that control NK cell responses in this immune-privileged site. We show that the constitutive expression of IFNε in the uterus plays a crucial role in promoting the accumulation, activation, and IFNγ production of NK cells in uterine tissue during Chlamydia infection. Uterine epithelial IFNε primes NK cell responses indirectly by increasing IL-15 production by local immune cells and directly by promoting the accumulation of a pre-pro-like NK cell progenitor population and activation of NK cells in the uterus. These findings demonstrate the unique features of this uterine-specific type I IFN and the mechanisms that underpin its major role in orchestrating innate immune cell protection against uterine infection.

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http://hdl.handle.net/10453/179902