Thymic stromal lymphopoietin (TSLP) is a potent pro-inflammatory mediator which is epigenetically deregulated in endometriosis

Soolmaz Habibi, Ramazanali F, Fariba Ramazanali, Raha Favaedi, Favaedi R, Afsharian P, Parvaneh Afsharian, Elham Amirchaghmaghi, Amirchaghmaghi E, Maryam Shahhoseini, Shahhoseini M
Journal of reproductive immunology · 2022 · vol. 151 , pp. 103515 · doi:10.1016/j.jri.2022.103515 · PMID:35381481 · W4220965982
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This study investigated thymic stromal lymphopoietin (TSLP) as a pro-inflammatory mediator, finding that its expression is epigenetically deregulated in endometriosis.

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Abstract

ObjectiveEndometriosis is an estrogen-dependent disease characterized by the presence of endometriotic tissue outside the uterine cavity, the condition that immunological factors play important roles in its pathogenesis. Thymic stromal lymphopoietin (TSLP) is an interleukin 7-like cytokine that triggers dendritic cell-mediated T helper2 inflammatory responses. TSLP receptor, or cytokine receptor- like factor 2 (CRLF2), forms a functional heterodimeric complex with IL-7 receptor alpha (IL-7Rα) to bind with TSLP. The present study aimed to elucidate the expression and epigenetic alterations of TSLP gene parallel to TSLP receptor and IL-10 genes expression in endometrial tissues of patients with endometriosis compared to controls.Materials & methodsIn this case-control study, 45 women with and without endometriosis was enrolled. The relative expression of TSLP, TSLPR and IL-10 genes were examined using qPCR. Chromatin Immunoprecipitation (ChIP) was also used to monitor epigenetic marks of methylation and acetylation on lysine 9 of histone H3 (H3K9me/ac) and DNA methylation in TSLP promoter.Results and conclusionTSLP, TSLPR and IL-10 genes were overexpressed in ectopic endometriotic lesions compared to controls. In ectopic samples, significant H3K9 hyper-acetylation and hypo-methylation parallel to DNA hypo-methylation were detected in TSLP promoter compared to eutopic and control groups (p < 0.05). These epigenetic changes were aligned with TSLP gene expression profile. These data collectively identify TSLP and TSLPR as candidate genes critically involved in development of endometriosis beyond their role in promoting Th2 immune responses. In addition, acetylation and methylation of H3K9 may have effective roles in TSLP dysregulation in endometriosis.

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Condition tags

endometriosis

MeSH descriptors

Cytokines Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Case-Control Studies Case-Control Studies Case-Control Studies Case-Control Studies Case-Control Studies Case-Control Studies Cytokines Cytokines Cytokines Cytokines Cytokines Cytokines

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