Enhanced local and systemic inflammatory cytokine mRNA expression in women with endometriosis evokes compensatory adaptive regulatory mRNA response that mediates immune suppression and impairs cytotoxicity

Emma Björk, Emma M. Björk, Marie‐Therese Vinnars, Marie-Therese Vinnars, Ivan Nagaev, Olga Nagaeva, Eva Lundin, Ulrika Ottander, Lucia Mincheva‐Nilsson
American journal of reproductive immunology (New York, N.Y. : 1989) · 2020 · vol. 84(4) , pp. e13298 · doi:10.1111/aji.13298 · PMID:32623813 · W3038331063
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Abstract

PROBLEM: Endometriosis is a disease characterized by ectopic implantation of endometrium and impaired immune responses. To explore its pathogenic mechanisms, we studied the local and systemic cytokine mRNA profiles and their role in the immunity of patients with endometriosis and healthy controls. METHOD OF STUDY: mRNA for eleven cytokines defining cytotoxic Th1, humoral Th2, regulatory Tr1/Th3, and inflammatory cytokine profiles was characterized locally in endometriotic tissue and endometrium, and systemically in PBMCs from women with endometriosis and healthy controls, using real-time qRT-PCR. In addition, immunohistochemical stainings with monoclonal antibodies were performed looking for T regulatory cells in endometriotic lesions. RESULTS: We found a downregulation of mRNA for cytokines mediating cytotoxicity and antibody response and an upregulation of inflammatory and T-regulatory cytokines in the endometriotic tissues and endometrium from the patients with endometriosis, suggesting enhanced local inflammation and priming of an adaptive regulatory response. Consistent with those findings, there was an abundancy of T regulatory cells in the endometriotic lesions. CONCLUSIONS: The ectopic implantation seen in endometriosis could be possible as a consequence of increased inflammation and priming of adaptive T regulatory cells, resulting in impaired cytotoxicity and enhanced immune suppression.

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endometriosis

MeSH descriptors

Cytokines Endometriosis Endometrium Inflammation Inflammation Mediators RNA, Messenger T-Lymphocytes, Regulatory Adaptive Immunity Adult Cytokines Cytotoxicity, Immunologic Endometriosis Endometrium Female Humans Immune Tolerance Inflammation Inflammation Mediators Middle Aged RNA, Messenger

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