Accumulation of IL‐17⁺ Vγ6⁺ γδ T cells in pregnant mice is not associated with spontaneous abortion

<jats:title>Abstract</jats:title><jats:sec><jats:title>Introduction</jats:title><jats:p>Pregnancy is an immune paradox. While the immune system is required for embryo implantation, placental development and progression of gestation, excessive inflammation is associated with pregnancy failure. Similarly, the cytokine <jats:styled-content style="fixed-case">IL</jats:styled-content>‐17A plays an important role in defence against extracellular pathogens, but its dysregulation can lead to pathogenic inflammation and tissue damage. Although expression of <jats:styled-content style="fixed-case">IL</jats:styled-content>‐17 has been reported during pregnancy, the cellular source of this cytokine and its relevance to gestation are not clear.</jats:p></jats:sec><jats:sec><jats:title>Objectives</jats:title><jats:p>Here we define the kinetics and cellular source of <jats:styled-content style="fixed-case">IL</jats:styled-content>‐17A in the uterus during healthy and abortion‐prone murine pregnancy.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>The <jats:styled-content style="fixed-case">CBA</jats:styled-content>/J x <jats:styled-content style="fixed-case">DBA</jats:styled-content>/2J abortion‐prone mating was used and compared to <jats:styled-content style="fixed-case">CBA</jats:styled-content>/J x <jats:styled-content style="fixed-case">BALB</jats:styled-content>/c control mating.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>We demonstrate that, irrespective of gestational health, the number of <jats:styled-content style="fixed-case">IL</jats:styled-content>‐17‐producing cells peaks during midterm pregnancy and is largely derived from the γδ T‐cell lineage. We identify γδ T, Th17, <jats:styled-content style="fixed-case">CD</jats:styled-content>8 T and <jats:styled-content style="fixed-case">NKT</jats:styled-content> cells as the cellular source of <jats:styled-content style="fixed-case">IL</jats:styled-content>‐17A in pregnant mice. Furthermore, we positively identify the Vγ6<jats:sup>+</jats:sup> subset of uterine γδ T cells as the main producer of <jats:styled-content style="fixed-case">IL</jats:styled-content>‐17A during both healthy pregnancy and abortive pregnancy.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>To conclude, the accumulation of uterine <jats:styled-content style="fixed-case">IL</jats:styled-content>‐17<jats:sup>+</jats:sup> innate‐like T cells appears not to adversely impact the developing foetus. Collectively, our results show that <jats:styled-content style="fixed-case">IL</jats:styled-content>‐17<jats:sup>+</jats:sup> γδ T cells are present in the uterus throughout the course of normal gestation and therefore may play an important role in healthy pregnancy.</jats:p></jats:sec>