EMBO Molecular Medicine (Jan 2024)
Interferon-epsilon is a novel regulator of NK cell responses in the uterus
- 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,
- Philip M Hansbro
Affiliations
- Jemma R Mayall
- Immune Health Program, Hunter Medical Research Institute and the University of Newcastle
- Jay C Horvat
- Immune Health Program, Hunter Medical Research Institute and the University of Newcastle
- Niamh E Mangan
- Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research and Departments of Molecular and Translational Sciences, Monash University
- Anne Chevalier
- Immune Health Program, Hunter Medical Research Institute and the University of Newcastle
- Huw McCarthy
- Immune Health Program, Hunter Medical Research Institute and the University of Newcastle
- Daniel Hampsey
- Immune Health Program, Hunter Medical Research Institute and the University of Newcastle
- Chantal Donovan
- Centre for Inflammation, Centenary Institute and University of Technology Sydney, Faculty of Science, School of Life Sciences
- Alexandra C Brown
- Immune Health Program, Hunter Medical Research Institute and the University of Newcastle
- Antony Y Matthews
- Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research and Departments of Molecular and Translational Sciences, Monash University
- Nicole A de Weerd
- Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research and Departments of Molecular and Translational Sciences, Monash University
- Eveline D de Geus
- Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research and Departments of Molecular and Translational Sciences, Monash University
- Malcolm R Starkey
- Immune Health Program, Hunter Medical Research Institute and the University of Newcastle
- Richard Y Kim
- Immune Health Program, Hunter Medical Research Institute and the University of Newcastle
- Katie Daly
- Immune Health Program, Hunter Medical Research Institute and the University of Newcastle
- Bridie J Goggins
- Immune Health Program, Hunter Medical Research Institute and the University of Newcastle
- Simon Keely
- Immune Health Program, Hunter Medical Research Institute and the University of Newcastle
- Steven Maltby
- Immune Health Program, Hunter Medical Research Institute and the University of Newcastle
- Rennay Baldwin
- Immune Health Program, Hunter Medical Research Institute and the University of Newcastle
- Paul S Foster
- Immune Health Program, Hunter Medical Research Institute and the University of Newcastle
- Michael J Boyle
- Immune Health Program, Hunter Medical Research Institute and the University of Newcastle
- Pradeep S Tanwar
- Gynecology Oncology Research Group, School of Biomedical Sciences and Pharmacy, University of Newcastle
- Nicholas D Huntington
- Monash Biomedicine Discovery Institute, Monash University
- Paul J Hertzog
- Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research and Departments of Molecular and Translational Sciences, Monash University
- Philip M Hansbro
- Immune Health Program, Hunter Medical Research Institute and the University of Newcastle
- DOI
- https://doi.org/10.1038/s44321-023-00018-6
- Journal volume & issue
-
Vol. 16,
no. 2
pp. 267 – 293
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.
Keywords
- Interferon-Epsilon
- Type I Interferon
- Natural Killer Cell
- Female Reproductive Tract
- Chlamydia Infection
