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

Jemma R MayallJay C HorvatNiamh E ManganAnne ChevalierHuw McCarthyDaniel HampseyChantal DonovanAlexandra C BrownAntony Y MatthewsNicole A de WeerdEveline D de GeusMalcolm Ronald StarkeyRichard Y KimKatie DalyBridie J GogginsSimon KeelySteven MaltbyRennay BaldwinPaul S FosterMichael J BoylePradeep S TanwarNicholas D HuntingtonPaul J HertzogPhilip Michael Hansbro
Published in: EMBO molecular medicine (2024)
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.
Keyphrases
  • nk cells
  • immune response
  • dendritic cells
  • poor prognosis
  • toll like receptor