Exacerbation of Endometriosis Due To Regulatory T-Cell Dysfunction

Yukiko Tanaka, Tanaka Y, Taisuke Mori, Ito F, Fumitake Ito, Akemi Koshiba, Koshiba A, Osamu Takaoka, Takaoka O, Hisashi Kataoka, Maeda E, Eiko Maeda, Okimura H, Hiroyuki Okimura, Takahide Mori, Mori T, Jo Kitawaki, Kitawaki J
The Journal of clinical endocrinology and metabolism · 2017 · vol. 102(9) , pp. 3206–3217 · doi:10.1210/jc.2017-00052 · PMID:28575420 · W2617143885
Other OA: bronze CC0 ⤵ 66 in-corpus citations
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This study found that a decrease in activated regulatory T cells in women with endometriosis and in a mouse model correlates with increased inflammation, angiogenesis, and endometriotic lesion growth.

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Abstract

CONTEXT: Endometriosis is a chronic inflammatory disease associated with altered immune response to endometrial cells facilitating the implantation and proliferation of ectopic endometrial tissues. Although regulatory T (Treg) cells play a key role in T cell-mediated immune response and development of immune disorders, their significance in endometriosis remains to be elucidated. Recently, CD4+CD45RA- forkhead box protein 3 (Foxp3)hi T cells, activated Treg cells, have been identified as a functionally true suppressive population of Treg cells. OBJECTIVE: To investigate the role of Treg cells in endometriosis. DESIGN: Three Treg cell fractions (resting Treg cells, activated Treg cells, and non-Treg cells) were examined using flow cytometry in the endometrioma, endometrium, peritoneal fluid, and peripheral blood obtained from women with (n = 27) and without (n = 28) endometriosis. A mouse model of endometriosis was made in Foxp3tm3Ayr/J (Foxp3DTR) C57BL/6 Treg cell-depleted mice (n = 28). RESULTS: In women with endometrioma, the proportion of activated Treg cells in the endometrioma and the endometrium, but not in the peritoneal fluid or peripheral blood, was significantly decreased compared with that in women without endometriosis. In Foxp3DTR/diphtheria toxin mice, the number and weight of endometriotic lesions, inflammatory cytokine levels and angiogenetic factors were significantly increased compared with those in control mice. CONCLUSIONS: Treg cell deficiency exaggerates local inflammation and angiogenesis and simultaneously facilitates the attachment and growth of endometrial implants. The findings provide an insight into dysregulated immune response for the pathogenesis and development.

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Condition tags

endometriosisendometrioma

MeSH descriptors

Disease Progression Disease Progression Endometriosis Forkhead Transcription Factors Immunity, Cellular Immunity, Cellular T-Lymphocytes, Regulatory Adult Adult Analysis of Variance Analysis of Variance Animals Animals Ascitic Fluid Ascitic Fluid Ascitic Fluid Disease Models, Animal Disease Models, Animal Endometriosis Endometriosis

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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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Cited by (50)

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