Thymic stromal lymphopoietin contributes to endometriotic lesion proliferation and disease-associated inflammation
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Authors
Aleksieva, Stanimira
Date
2024-06-25
Type
thesis
Language
eng
Keyword
Endometriosis , Thymic stromal lymphopoietin
Alternative Title
Abstract
Endometriosis is a chronic disorder in which endometrial-like tissue establishes outside the uterus. Patients with endometriosis have been shown to exhibit aberrant immune responses within the lesion microenvironment and in circulation which contribute to the development of endometriosis. This includes the predominance of Th2 immune responses that prevent lesion clearance and enhance lesion proliferation and angiogenesis. Thymic stromal lymphopoietin (TSLP) is an alarmin involved in cell proliferation and the induction of Th2 inflammation. This contributes to pathogenesis of various diseases, such as asthma, atopic dermatitis, pancreatic and breast cancer. Recent studies have detected TSLP within endometriotic lesions and shown that its concentrations are elevated in the peritoneal fluid and serum of patients compared to controls. However, its role in disease pathophysiology remains unclear. Here, we compared TSLP expression in endometriotic lesions to matched patient endometrium and control endometrium samples by performing immunohistochemistry on a tissue microarray. We also assessed its effect on the proliferation and apoptosis of human endometriosis-representative cell lines through calorimetric assays, as well as on lesion development and inflammation in a C57BL/6 mouse model of the disease. We demonstrated that TSLP expression was elevated in the stroma of patient endometriotic lesions compared to control endometrial samples. In cell lines, TSLP treatment reduced the apoptosis of endometrial stromal cells and promoted the proliferation of THP-I cells. In mice induced with endometriosis, TSLP treatment induced a Th2 immune response within the lesion microenvironment, and led to TSLP receptor modulation in macrophages, dendritic cells, and CD4+ T cells. Furthermore, treatment increased murine endometriotic lesion proliferation, but had no detectable effect on angiogenesis. Overall, these results suggest that TSLP modulates the endometriotic lesion microenvironment and promotes a Th2 immune response that could support lesion development.
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This publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.
Attribution-NonCommercial-NoDerivatives 4.0 International
ProQuest PhD and Master's Theses International Dissemination Agreement
Intellectual Property Guidelines at Queen's University
Copying and Preserving Your Thesis
This publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.
Attribution-NonCommercial-NoDerivatives 4.0 International