Seminal plasma induces inflammation in the uterus through the γδ T/IL-17 pathway

Song, Zhihui; Li, Zhongyi; Li, Dandan; Fang, Wen-Ning; Liu, Haiyan; Yang, Dandan; Meng, Chunlei; Yang, Ying; Peng, Jing‐Pian

doi:10.1038/srep25118

Cited by 41 publications

(34 citation statements)

References 48 publications

(58 reference statements)

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“…Following insemination of naive mice, a large number of leukocytes migrate into the uterus accumulating around the uterine epithelium. The seminal plasma sensitizes the γδ T‐cells, which secrete IL17A, thereby inducing inflammation regulating the expression of different chemokines and cytokines (Song et al, ). This triggers the activation and expansion of T‐ and B‐lymphocytes and NK cells enhancing of cytokine expression, for example, IL2, IL4, and IFNA to mediate maternal tolerance at the implantation site (Johanson, Bromfield, Jasper, & Robertson, ).…”

Section: Testicular Immune Mechanismmentioning

confidence: 99%

Immune regulatory molecules as modifiers of semen and fertility: A review

Archana

Selvaraju

Binsila

et al. 2019

Molecular Reproduction Devel

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Declining fertility rates in both human and animals is a cause for concern. While many of the infertility cases are due to known causes, idiopathic infertility is reported in 30% of the infertile couples. In such cases, 18% of the infertile males carry antisperm antibodies (ASAs). Such data are lacking in livestock, wherein 20–30% of the animals are being culled due to low fertility. In males, the blood–testis barrier (BTB) and biomolecules in the semen provide an immuno‐tolerant microenvironment for spermatozoa as they traverse the immunologic milieu of both the male and female reproductive tracts. For example, insults from environmental contaminants, infections and inflammatory conditions are likely to impact the immune privilege state of the testis and fertility. The female mucosal immune system can recognize allogenic spermatozoa‐specific proteins affecting sperm kinematics and sperm‐zona binding leading to immune infertility. Elucidating the functions and pathways of the immune regulatory molecules associated with fertilization are prerequisites for understanding their impact on fertility. An insight into biomolecules associated with spermatozoal immune tolerance may generate inputs to develop diagnostic tools and modulate fertility. High‐throughput sequencing technologies coupled with bioinformatics analyses provides a path forward to define the array of molecules influencing pregnancy outcome. This review discusses the seminal immune regulatory molecules from their origin in the testis until they traverse the uterine environment enabling fertilization and embryonic development. Well‐designed experiments and the identification of biomarkers may provide a pathway to understand the finer details of reproductive immunology that will afford personalized therapies.

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Section: Testicular Immune Mechanismmentioning

confidence: 99%

Immune regulatory molecules as modifiers of semen and fertility: A review

Archana

Selvaraju

Binsila

et al. 2019

Molecular Reproduction Devel

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“…In non-pregnant individuals, neutrophils can be found in the cervix, endometrium and fallopian tubes (65, 66) while in pregnant women neutrophils additionally invade the decidua, placenta, and fetal membranes (67,68). At insemination neutrophils specifically migrate and accumulate around the uterine epithelium (69). Here, they overtake various critical functions associated with angiogenesis, uSA remodeling and trophoblast invasion (70, 71) ( Figure 1D).…”

Section: Neutrophilsmentioning

confidence: 99%

Human Chorionic Gonadotropin-Mediated Immune Responses That Facilitate Embryo Implantation and Placentation

Schumacher

Zenclussen

2019

Front. Immunol.

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Human chorionic gonadotropin (hCG) serves as one of the first signals provided by the embryo to the mother. Exactly at the time when the first step of the implantation process is initiated and the blastocyst adheres to the maternal endometrium, the embryonic tissue starts to actively secrete hCG. Shortly thereafter, the hormone can be detected in the maternal circulation where its concentration steadily increases throughout early pregnancy as it is continuously released by the forming placenta. Accumulating evidence underlines the critical function of hCG for embryo implantation and placentation. hCG not only regulates biological aspects of these early pregnancy events but also supports maternal immune cells in their function as helpers in the establishment of an adequate embryo-endometrial relationship. In view of its early presence in the maternal circulation, hCG has the potential to influence both local uterine immune cell populations as well as peripheral ones. The current review aims to summarize recent literature on the participation of innate and adaptive immune cells in embryo implantation and placentation with a specific focus on their regulation by hCG.

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“…Early studies suggested that IL‐17 was associated with complications during pregnancy and infertility . However, more recent studies suggest a beneficial function for IL‐17 during pregnancy including the promotion of embryo implantation . Importantly, new biologics targeting IL‐17A and its receptor have shown clinical efficacy in the treatment of psoriatic disease and rheumatoid arthritis .…”

Section: Introductionmentioning

confidence: 99%

“…[5][6][7] However, more recent studies suggest a beneficial function for IL-17 during pregnancy including the promotion of embryo implantation. [8][9][10] Importantly, new biologics targeting IL-17A and its receptor have shown clinical efficacy in the treatment of psoriatic disease and rheumatoid arthritis. 3 Given the prevalence of these diseases in the female population and the requirement for lifelong use of these medications to prevent disease progression, understanding the impact of this cytokine pathway on pregnancy is vital for reproductive health.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2018

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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.

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Seminal plasma induces inflammation in the uterus through the γδ T/IL-17 pathway

Cited by 41 publications

References 48 publications

Immune regulatory molecules as modifiers of semen and fertility: A review

Immune regulatory molecules as modifiers of semen and fertility: A review

Human Chorionic Gonadotropin-Mediated Immune Responses That Facilitate Embryo Implantation and Placentation

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

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Seminal plasma induces inflammation in the uterus through the γδ T/IL-17 pathway

Cited by 41 publications

References 48 publications

Immune regulatory molecules as modifiers of semen and fertility: A review

Immune regulatory molecules as modifiers of semen and fertility: A review

Human Chorionic Gonadotropin-Mediated Immune Responses That Facilitate Embryo Implantation and Placentation

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

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