CD4⁺ T cell imbalance is associated with recurrent endometrial polyps

Abstract

Endometrial polyps (EPs) are localized benign overgrowths at the endometrium, with currently unknown aetiology and pathogenesis. Although symptoms of EP can be alleviated or resolved by hysteroscopic polypectomy, a significant fraction of individuals develop recurrent EPs after initial EP removal. In rare cases, EPs may also undergo malignant transformation. In-depth understanding of the mechanisms that are involved in EP development is urgently needed. Recent works indicate that dysregulations in the immune system participate in the development of a variety of symptoms, such as aging, obesity and hypertension, many of which are EP risk factors. Based on these discoveries, we investigated the cellular immune system in premenopausal women with and without EP. Compared to EP-free controls, the women with EP presented significantly higher RORC expression but unchanged TBX21 and FOXP3 expression in the circulating CD4 T cells. When stimulated with PMA/ionomycin, CD4 T cells from women with EP presented significantly higher interferon (IFN)-γ and interleukin (IL)-17 secretion, and lower transforming growth factor (TGF)-β secretion. Hysteroscopic polypectomy did not significantly alter the composition of CD4 T cells, as the women with EP presented a similar upregulation of Th17 inflammation and a downregulation of regulatory T cell (Treg) response postoperatively. Notably, in women that developed recurrent EP, the CD4 T cells presented higher preoperative and postoperative RORC, IFN-γ, and IL-17 expression, as well as lower postoperative FOXP3 and TGF-β expression, than hysteroscopic polypectomy-treated women without EP recurrence. These data demonstrated an association between CD4 T cell imbalance and recurrent EP development.

TGF-β1 role in uterine leiomyoma and endometrial polyp: an insight to drug-based treatment instead of surgical techniques

“…They reported a correlation between high levels of metalloproteinase and interleukin 1, but not TGF-β, in polyp irrigation samples. In line with Zhu et al [10] and incongruent to Xuebing et al [20], based on our study, polyp lesions showed no TGF-β1 presentation, while 10.9% of normal endometrium expressed this cytokine with no significant statistical difference.…”

“…They also demonstrated that stromal cells of the endometrium express this cytokine in a lower amount than glandular cells independent of menstrual cycles. Moreover, Zhu et al [10] presented low concentrations of TGF-β among patients with polyps. Inagaki et al [18] surveyed the level of cytokines in uterine cavity irrigation samples in patients with polyps.…”

“…Obstet Gynecol Sci 2020 Nov 26. [Epub ahead of print] cause AUB [9]. Although its definite cause is unknown, some hormonal imbalance, immune mechanisms, and cytokines such as TGF-β (mainly TGF-β1) are attributed to polyp development [10][11][12][13].…”

Multiple endometrial polyps is associated with higher risk of chronic endometritis in reproductive‐aged women

“…Increasing evidence suggests that an inflammatory component should be considered, at least in a subset of polyps 11 . Classical inflammatory‐associated factors, including NF‐κB, IFN‐γ and IL‐17, 8–10 are activated in polyps, along with vascular changes secondary to endometritis 19 . The local disturbance in the cellular immune environment observed in EP, such as excess mast cell activity and increased expression of c‐Kit, also suggests that EP are inflammatory lesions 20 .…”

“…Emerging evidence has shown that the heterogeneity of the EP subtype may be due to a multifactorial pathogenesis 7 . In addition to estrogen dysregulation, chronic endometrial inflammation was thought to be another contributor to EP development as inflammatory cytokines such as NF‐κB, 8 IFN‐γ and IL‐17 9,10 were activated in polyps. Moreover, endometrial micropolyps were found to have skewed local mononuclear cell composition compared with estrogen‐dependent macropolyps and co‐existed with endometritis 11 .…”