CD4+ T cell imbalance is associated with recurrent endometrial polyps

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.