Deep Infiltrating Endometriosis and Activation and Memory Surface Markers and Cytokine Expression in Isolated Treg Cells

article OA: closed CC0 ⤵ 10 in-corpus citations
AI-generated summary by claude@2026-06+body, 2026-06-28

Regulatory T cells from women with deep endometriosis show distinct activation and memory marker profiles in peripheral blood and peritoneal fluid, but similar cytokine mRNA expression.

One-sentence paraphrase of the abstract; not a substitute for reading it. No clinical advice. How this works

Full text 8,101 characters · extracted from oa-doi-fallback · 2 sections · click to expand

Abstract

It is not yet clear whether regulatory T (Treg) cells are active, and whether they play a favorable or adverse effect on endometrial foci implantation. Our aim was to evaluate activation and memory surface markers in Treg isolated from peritoneal fluid (PF) and peripheral blood (PB) of women with deep endometriosis and to assess its cytokine mRNA expression. This case-control study included 49 women with deep infiltrating endometriosis and 20 healthy controls. It was analyzed PF and PB of both groups. Cell surface markers GITR, TNFRII, HLA-DR, ICOS, CTLA-4, CD45RA, and CD45RO were evaluated in Treg (CD3+CD4+CD25+CD127lowFoxp3+) cells by flow cytometry. Additionally, Foxp3, TGF-beta, IL-10, IL-6, and TNF-alpha mRNA expression was assessed by real-time PCR in Treg cells (CD4+CD25+CD127dim/−) isolated using magnetic microbeads. Women with endometriosis had higher percentages of TNFRII+ Treg and CTLA-4+ Treg in their PB, and lower percentages of ICOS+ Treg and CD45RO+ Treg in their PF. The groups displayed no differences in mRNA expression. Regardless of the group, in PF, the percentage of Treg cells overall and of CD45RA+ Treg cells were significantly lower, whereas the percentage of TNFRII+ Treg and CD45RO+ Treg were significantly higher than in PB. Foxp3 and TGF-beta mRNA expression were also higher in PF than in PB. Our results indicated that Treg cells in women with endometriosis have a distinct profile of activation and memory markers, but similar cytokine expression. Moreover, we could observe clearly that Treg cells have distinct profile regarding their origin site. Similar content being viewed by others

References

Giudice LC. Clinical practice. Endometriosis. N Engl J Med. 2010;362:2389–98. Abrao MS, Petraglia F, Falcone T, Keckstein J, Osuga Y, Chapron C. Deep endometriosis infiltrating the recto-sigmoid: critical factors to consider before management. Hum Reprod Update. 2015;21:329–39. Olovsson M. Immunological aspects of endometriosis: an update. Am J Reprod Immunol. 2011;66(Suppl 1):101–4. Burney RO, Giudice LC. Pathogenesis and pathophysiology of endometriosis. Fertil Steril. 2012;98:511–9. de Barros IBL, Malvezzi H, Gueuvoghlanian-Silva BY, Piccinato CA, Rizzo LV, Podgaec S. What do we know about regulatory T cells and endometriosis? A systematic review. J Reprod Immunol. 2017;120:48–55. de Barros IBL, Malvezzi H, Gueuvoghlanian-Silva BY, Piccinato CA, Rizzo LV, Podgaec S. Corrigendum to “What do we know about regulatory T cells and endometriosis? A systematic review”. J Reprod Immunol. 2017;120:48–55 J Reprod Immunol 2017;121:34. Wan YY, Flavell RA. ‘Yin-Yang’ functions of transforming growth factor-beta and T regulatory cells in immune regulation. Immunol Rev. 2007;220:199–213. Josefowicz SZ, Lu LF, Rudensky AY. Regulatory T cells: mechanisms of differentiation and function. Annu Rev Immunol. 2012;30:531–64. Attridge K, Walker LS. Homeostasis and function of regulatory T cells (Tregs) in vivo: lessons from TCR-transgenic Tregs. Immunol Rev. 2014;259:23–39. Mjosberg J, Berg G, Jenmalm MC, Ernerudh J. FOXP3+ regulatory T cells and T helper 1, T helper 2, and T helper 17 cells in human early pregnancy decidua. Biol Reprod. 2010;82:698–705. Faget J, Bendriss-Vermare N, Gobert M, Durand I, Olive D, Biota C, et al. ICOS-ligand expression on plasmacytoid dendritic cells supports breast cancer progression by promoting the accumulation of immunosuppressive CD4+ T cells. Cancer Res. 2012;72:6130–41. Angin M, King M, Addo MM. New tools to expand regulatory T cells from HIV-1-infected individuals. J Vis Exp 2013. Askenasy N, Kaminitz A, Yarkoni S. Mechanisms of T regulatory cell function. Autoimmun Rev. 2008;7:370–5. Weiss G, Goldsmith LT, Taylor RN, Bellet D, Taylor HS. Inflammation in reproductive disorders. Reprod Sci. 2009;16:216–29. Zhou L, Chong MM, Littman DR. Plasticity of CD4+ T cell lineage differentiation. Immunity. 2009;30:646–55. Azuma M. Role of the glucocorticoid-induced TNFR-related protein (GITR)-GITR ligand pathway in innate and adaptive immunity. Crit Rev Immunol. 2010;30:547–57. Ronchetti S, Ricci E, Petrillo MG, et al. Glucocorticoid-induced tumour necrosis factor receptor-related protein: a key marker of functional regulatory T cells. J Immunol Res. 2015;2015:171520. Chen X, Oppenheim JJ. The phenotypic and functional consequences of tumour necrosis factor receptor type 2 expression on CD4(+) FoxP3(+) regulatory T cells. Immunology. 2011;133:426–33. Baecher-Allan C, Wolf E, Hafler DA. MHC class II expression identifies functionally distinct human regulatory T cells. J Immunol. 2006;176:4622–31. Gerdes N, Zirlik A. Co-stimulatory molecules in and beyond co-stimulation - tipping the balance in atherosclerosis? Thromb Haemost. 2011;106:804–13. Booth NJ, McQuaid AJ, Sobande T, et al. Different proliferative potential and migratory characteristics of human CD4+ regulatory T cells that express either CD45RA or CD45RO. J Immunol. 2010;184:4317–26. Callahan MK, Wolchok JD, Allison JP. Anti-CTLA-4 antibody therapy: immune monitoring during clinical development of a novel immunotherapy. Semin Oncol. 2010;37:473–84. Simpson TR, Quezada SA, Allison JP. Regulation of CD4 T cell activation and effector function by inducible costimulator (ICOS). Curr Opin Immunol. 2010;22:326–32. Wikenheiser DJ, Stumhofer JS. ICOS co-stimulation: friend or foe? Front Immunol. 2016;7:304. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 2001;25:402–8. Redpath SA, van der Werf N, Cervera AM, MacDonald A, Gray D, Maizels RM, et al. ICOS controls Foxp3(+) regulatory T-cell expansion, maintenance and IL-10 production during helminth infection. Eur J Immunol. 2013;43:705–15. Tanaka Y, Mori T, Ito F, et al. Exacerbation of endometriosis due to regulatory T-cell dysfunction. J Clin Endocrinol Metab. 2017;102:3206–17. Chen X, Subleski JJ, Kopf H, Howard OM, Mannel DN, Oppenheim JJ. Cutting edge: expression of TNFR2 defines a maximally suppressive subset of mouse CD4+CD25+FoxP3+ T regulatory cells: applicability to tumor-infiltrating T regulatory cells. J Immunol. 2008;180:6467–71. Tsakiri N, Papadopoulos D, Denis MC, Mitsikostas DD, Kollias G. TNFR2 on non-haematopoietic cells is required for Foxp3+ Treg-cell function and disease suppression in EAE. Eur J Immunol. 2012;42:403–12. Chen X, Subleski JJ, Hamano R, Howard OM, Wiltrout RH, Oppenheim JJ. Co-expression of TNFR2 and CD25 identifies more of the functional CD4+FOXP3+ regulatory T cells in human peripheral blood. Eur J Immunol. 2010;40:1099–106. Chen X, Du Y, Lin X, Qian Y, Zhou T, Huang Z. CD4+CD25+ regulatory T cells in tumor immunity. Int Immunopharmacol. 2016;34:244–9. Podgaec S, Rizzo LV, Fernandes LF, Baracat EC, Abrao MS. CD4(+) CD25(high) Foxp3(+) cells increased in the peritoneal fluid of patients with endometriosis. Am J Reprod Immunol. 2012;68:301–8. Peterson RA. Regulatory T-cells: diverse phenotypes integral to immune homeostasis and suppression. Toxicol Pathol. 2012;40:186–204. Pandiyan P, Zhu J. Origin and functions of pro-inflammatory cytokine producing Foxp3+ regulatory T cells. Cytokine. 2015;76:13–24. Funding We received financial from Fundacao de Amparo a Pesquisa do Estado de Sao Paulo, FAPESP (no. 2013/27092-2 and no. 2014/08227-7) and UNIEMP. Author information Authors and Affiliations Corresponding author Ethics declarations Conflict of Interest The authors declare that there is no conflict of interest. Additional information Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Rights and permissions About this article Cite this article Gueuvoghlanian-Silva, B.Y., Hernandes, C., Correia, R.P. et al. Deep Infiltrating Endometriosis and Activation and Memory Surface Markers and Cytokine Expression in Isolated Treg Cells. Reprod. Sci. 27, 599–610 (2020). https://doi.org/10.1007/s43032-019-00060-1 Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s43032-019-00060-1

Text is read by the "Ask this paper" AI Q&A widget below. Extraction quality varies by source — PMC NXML preserves structure cleanly, OA-HTML may include some navigation residue, and OA-PDF can have broken hyphenation. The publisher copy (via DOI) is the canonical version.

My notes (saved in your browser only)

Ask this paper AI returns verbatim quotes from the full text · source: oa-doi-fallback

Answers must be backed by verbatim quotes from this paper's full text. Hallucinated quotes are dropped automatically; if no verbatim passage answers the question, we say so. How this works

Condition tags

endometriosisdie_deep_infiltrating

MeSH descriptors

Cytokines Endometriosis T-Lymphocytes, Regulatory Adult Ascitic Fluid Ascitic Fluid Biomarkers Biomarkers Case-Control Studies Cytokines Endometriosis Female Humans RNA, Messenger RNA, Messenger T-Lymphocytes, Regulatory Young Adult

Citation neighborhood

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. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

References (37)

Cited by (10)

Source provenance

europepmc
last seen: 2026-07-02T06:07:54.402228+00:00
openalex
last seen: 2026-06-10T17:14:06.276822+00:00
pubmed
last seen: 2026-05-13T22:22:17.025735+00:00
unpaywall
last seen: 2026-06-13T06:42:57.164913+00:00
License: CC0 · commercial use OK