1. Interferon-epsilon is a novel regulator of NK cell responses in the uterus
- Author
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Jemma R Mayall, Jay C Horvat, Niamh E Mangan, Anne Chevalier, Huw McCarthy, Daniel Hampsey, Chantal Donovan, Alexandra C Brown, Antony Y Matthews, Nicole A de Weerd, Eveline D de Geus, Malcolm R Starkey, Richard Y Kim, Katie Daly, Bridie J Goggins, Simon Keely, Steven Maltby, Rennay Baldwin, Paul S Foster, Michael J Boyle, Pradeep S Tanwar, Nicholas D Huntington, Paul J Hertzog, and Philip M Hansbro
- Subjects
Interferon-Epsilon ,Type I Interferon ,Natural Killer Cell ,Female Reproductive Tract ,Chlamydia Infection ,Medicine (General) ,R5-920 ,Genetics ,QH426-470 - Abstract
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.
- Published
- 2024
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