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

Abstract

IntroductionPregnancy 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 IL‐17A plays an important role in defence against extracellular pathogens, but its dysregulation can lead to pathogenic inflammation and tissue damage. Although expression of IL‐17 has been reported during pregnancy, the cellular source of this cytokine and its relevance to gestation are not clear.ObjectivesHere we define the kinetics and cellular source of IL‐17A in the uterus during healthy and abortion‐prone murine pregnancy.MethodsThe CBA/J x DBA/2J abortion‐prone mating was used and compared to CBA/J x BALB/c control mating.ResultsWe demonstrate that, irrespective of gestational health, the number of IL‐17‐producing cells peaks during midterm pregnancy and is largely derived from the γδ T‐cell lineage. We identify γδ T, Th17, CD8 T and NKT cells as the cellular source of IL‐17A in pregnant mice. Furthermore, we positively identify the Vγ6+ subset of uterine γδ T cells as the main producer of IL‐17A during both healthy pregnancy and abortive pregnancy.ConclusionsTo conclude, the accumulation of uterine IL‐17+ innate‐like T cells appears not to adversely impact the developing foetus. Collectively, our results show that IL‐17+ γδ T cells are present in the uterus throughout the course of normal gestation and therefore may play an important role in healthy pregnancy.

Asthma and/or hay fever as predictors of fertility/impaired fecundity in U.S. women: National Survey of Family Growth

“…Prior to implantation 52,53 and in the peri-implantation period the fetal-maternal interface is also characterized by immune deviation to a proinflammatory 54 (IL-1beta, IL-6, LIF, PGE2, CXCL8, IL-17A, TNF) T2-low endotype 55–57 . Insemination, exposure to semen, initiates a short lived neutrophilic inflammatory (IL-1beta, TNF alpha, CxCL1, IL-17A) internal genital response 58–60 . The placental cytokines, IL-1beta, IL-6, TNFalpha, as well as increased PGE2 61,62 , are also associated with early onset (2 weeks after fertilization) pregnancy symptoms e.g., nausea/vomiting 62 .…”

Bacterial-induced maternal interleukin-17A pathway promotes autistic-like behaviors in mouse offspring

“…These acute phase responses of IL-17A suggest that pre-existing innate immune cells are the source of IL-17A rather than adaptive immune cells. It has been known that γδ T cells are enriched in the uterus during pregnancy to prevent intrauterine infection [3,20,21]. We found the augmentation of cell numbers of IL-17A-producing γδ T cells, but not its Th17 cells, in the uterus at 3 h post-injection of LPS.…”

“…Acute phase of IL-17A production at 3 h in LPS-injected MIA model implicated innate immune cells stimulated with LPS rather than adaptive immune cells. Previous reports indicate that γδ T cells as innate immune cells accumulate in mucosal sites for epithelial barrier roles [1,19] and are enriched in the uterus during pregnancy to prevent intrauterine infection [3,20,21]. Therefore, we first focused on γδ T cells in the uterus of LPS-injected pregnant mice.…”

γδ T cells compose a developmentally regulated intrauterine population and protect against vaginal candidiasis

“…T RM cells, and/or ageassociated changes in the uterine niche. While it is tempting to link this to sexual maturation, and despite the reported accumulation of γδ T cells at the maternal-fetal interface, 33,48,53 none of our studies strongly implicated γδ T cells in reproductive fitness. However, this is not to exclude discrete roles for local γδ T cells in other aspects of reproductive biology, e.g.…”