Interleukin-9 produced by helper T cells stimulates interleukin-8 expression in endometriosis

Yosuke Tarumi, Taisuke Mori, Okimura H, Hiroyuki Okimura, Maeda E, Eiko Maeda, Yukiko Tanaka, Tanaka Y, Hisashi Kataoka, Fumitake Ito, Ito F, Akemi Koshiba, Koshiba A, Kusuki I, Izumi Kusuki, Kitawaki J, Jo Kitawaki
American journal of reproductive immunology (New York, N.Y. : 1989) · 2020 · vol. 86(3) , pp. e13380 · doi:10.1111/aji.13380 · PMID:33210782 · W3103355677
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Helper T cell-produced IL-9 stimulates IL-8 expression in endometrial stromal cells, playing a significant role in endometriosis development.

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Abstract

PROBLEM: Inflammation and immune responses play crucial roles in the development of endometriosis. Although interleukin-9 (IL-9) has a pro-inflammatory function in chronic inflammatory diseases, its function in endometriosis remains unknown. Here, we aimed to investigate the significance of IL-9 and IL-9-producing lymphocytes in endometriosis. METHOD OF STUDY: Specimens were obtained from patients with and without endometriosis. Peritoneal fluid (PF), peripheral blood (PB), and ovarian endometrioma (OE) tissues were analyzed for the proportion of CD4+ IL-9+ lymphocytes and IL-9 concentration using flow cytometry and enzyme-linked immunosorbent assay. OE, endometrium with endometriosis (EE), and normal endometrium (NE) were analyzed for IL-9 receptor (IL-9R) expression using immunohistochemical staining. IL-9-dependent changes in Interleukin-8 (IL-8) expression in endometrial stromal cells from OE (OESCs) were evaluated using real-time PCR. RESULTS: The proportion of CD4+ IL-9+ lymphocytes was higher in the PF, but not the PB, of patients with endometriosis than individuals without endometriosis (p < .05). However, IL-9 levels in the PF did not differ between those with and without endometriosis. We detected CD4+ IL-9+ lymphocytes in OE tissues and IL-9R in OE tissues and OESCs. In OESC culture, IL-9 significantly elevated IL-8 expression in a dose-dependent manner (p < .05), which was nullified by the addition of the anti-IL-9 receptor antibody. Furthermore, IL-9 additively stimulated IL-8 expression in the presence of TNF-α (p < .05). CONCLUSION: Our findings show that IL-9 produced by helper T cells induces IL-8 expression, suggesting that IL-9 plays an important role in the development of endometriosis by stimulating IL-8 expression.

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Condition tags

endometriosis

MeSH descriptors

Endometriosis Interleukin-8 Interleukin-9 T-Lymphocytes, Helper-Inducer Adult Adult Endometriosis Endometriosis Female Female Humans Humans Interleukin-8 Interleukin-8 Interleukin-8 Interleukin-9 Interleukin-9 Interleukin-9 T-Lymphocytes, Helper-Inducer T-Lymphocytes, Helper-Inducer

Citation neighborhood (2-hop)

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. Outer rings show 2-hop neighbours — papers reached through the immediate citers/citees. [ collapse to 1-hop ]

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