Open AccessArticle
IL17A Suppresses IGFBP1 in Human Endometrial Stromal Cells
by
Susumu Tanaka, Misa Sawachika, Namika Yoshida, Kensuke Futani, Hiromi Murata and Hidetaka Okada
Reprod. Med. 2024, 5(2), 43-56; https://0-doi-org.brum.beds.ac.uk/10.3390/reprodmed5020006 (registering DOI) - 26 Apr 2024
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Abstract
Interleukin (IL) 17A has been implicated in preeclampsia, preterm labor, and miscarriage. IL17A production in non-lymphoid tissues is mainly carried out by unconventional γδ17T cells. Innate lymphoid cells (ILCs) 3, a subgroup of innate lymphocytes, can also be a source of IL17A in
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Interleukin (IL) 17A has been implicated in preeclampsia, preterm labor, and miscarriage. IL17A production in non-lymphoid tissues is mainly carried out by unconventional γδ17T cells. Innate lymphoid cells (ILCs) 3, a subgroup of innate lymphocytes, can also be a source of IL17A in the endometrium and are required from implantation to early pregnancy, with their regulation ensuring that pregnancy continues. Herein, we examined the expression of γδ17T cells and ILC3 regulators
IL1B,
IL23A, and
IL17D and IL17A receptors (
IL17RA/
IL17RC) in human endometrial stromal cells (EnSCs) and cell lines (KC02-44D). Accordingly, quantitative polymerase chain reaction and immunoblotting were employed.
IL1B,
IL23A, and
IL17D were significantly upregulated in decidualized EnSCs and KC02-44D cells. A significant augmentation in
IL17RA/
IL17RC was also observed in decidualization. IL17A stimulation of KC02-44D cells during decidualization suppressed the decidualization marker
IGFBP1. The involvement of transcription factor Forkhead box protein O1 (FOXO1) in this repression was reflected by its translocation from the nucleus into the cytoplasm. A role for IkB kinase alpha in FOXO1 phosphorylation-mediated migration was also suggested. Taken together, our findings indicate that the secretion of IL17A by γδ17T and ILC3 cells in the uterus contributes to EnSCs function and may play critical roles in regulating IGFBP1-mediated implantation and fetal growth.
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