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

Abstract

After insemination, a large number of leukocytes migrate into the uterus, which is accompanied by intense inflammation. However, the details of how seminal plasma interacts with the uterus are still not very clear. Here, we present that neutrophils migrate and accumulate around the uterine epithelium following insemination, which is accompanied by an increase in interleukin (IL) 17A levels. Additionally, we find that γδ T cells are the major source of IL-17A, and the seminal plasma could induce the γδ T cells to secret IL-17A. Blocking IL-17A could reduce the number of neutrophils in the uterus and prevent them from migrating to the epithelium by decreasing the chemokines CXCL1, CXCL2 and CXCL5. Blocking IL-17A did not affect the Th1/Th2 balance but actually diminished the inflammation in the uterus by reducing the expression of IL-1β and TNF-α. In summary, we found a new mechanism by which seminal plasma could influence the inflammation in the uterus through the γδ T/IL-17 pathway to regulate the expression of various chemokines and cytokines.

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

“…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, ).…”

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

“…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).…”

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

“…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 .…”

“…[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.…”