Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

ACC 2024 Congress

Catch up on all the top stories and latest evidence in cardiology research with our ACC 2024 Congress hub page.
ADVANCED SEARCH
Log in
Top
Reproductive Biology and Endocrinology
Published in: Reproductive Biology and Endocrinology 1/2018

Open Access 01-12-2018 | Research

Suppressive regulatory T cells and latent transforming growth factor-β-expressing macrophages are altered in the peritoneal fluid of patients with endometriosis

Authors: Tetsuro Hanada, Shunichiro Tsuji, Misako Nakayama, Shiro Wakinoue, Kyoko Kasahara, Fuminori Kimura, Takahide Mori, Kazumasa Ogasawara, Takashi Murakami

Published in: Reproductive Biology and Endocrinology | Issue 1/2018

Login to get access

Abstract

Background

Endometriosis is a known cause of infertility. Differences in immune tolerance caused by regulatory T cells (Tregs) and transforming growth factor-β (TGF-β) are thought to be involved in the pathology of endometriosis. Evidence has indicated that Tregs can be separated into three functionally and phenotypically distinct subpopulations and that activated TGF-β is released from latency-associated peptide (LAP) on the surfaces of specific cells. The aim of this study was to examine differences in Treg subpopulations and LAP in the peripheral blood (PB) and peritoneal fluid (PF) of patients with and without endometriosis.

Methods

PB and PF were collected from 28 women with laparoscopically and histopathologically diagnosed endometriosis and 20 disease-free women who were subjected to laparoscopic surgery. Three subpopulations of CD4+ T lymphocytes (CD45RA+FoxP3low resting Tregs, CD45RA−FoxP3high effector Tregs, and CD45RA−FoxP3low non-Tregs) and CD11b+ mononuclear cells expressing LAP were analyzed by flow cytometry using specific monoclonal antibodies.

Results

Proportions of suppressive Tregs (resting and effector Tregs) were significantly higher in the PF samples of patients with endometriosis than in those of control women (P = 0.02 and P < 0.01, respectively) but did not differ between the PB samples of patients and controls. The percentage of CD11b+LAP+ macrophages was significantly lower in PF samples of patients with endometriosis than in those of controls (P < 0.01) but was not altered in the PB samples.

Conclusion

Proportions of suppressive Tregs and LAP+ macrophages are altered locally in the PF of endometriosis patients.
Appendix
Available only for authorised users
Literature
1.
2.
Sakaguchi S, Yamaguchi T, Nomura T, Ono M. Regulatory T cells and immune tolerance. Cell. 2008;133:775–87.CrossRefPubMed
3.
Curiel TJ, Coukos G, Zou L, Alvarez X, Cheng P, Mottram P, et al. Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med. 2004;10:942–9.CrossRefPubMed
4.
Ehrenstein MR, Evans JG, Singh A, Moore S, Warnes G, Isenberg DA, et al. Compromised function of regulatory T cells in rheumatoid arthritis and reversal by anti-TNFalpha therapy. J Exp Med. 2004;200:277–85.CrossRefPubMedPubMedCentral
5.
Miyara M, Amoura Z, Parizot C, Badoual C, Dorgham K, Trad S, et al. Global natural regulatory T cell depletion in active systemic lupus erythematosus. J Immunol. 2005;175:8392–400.CrossRefPubMed
6.
Miyara M, Sakaguchi S. Human FoxP3(+)CD4(+) regulatory T cells: their knowns and unknowns. Immunol Cell Biol. 2011;89:346–51.CrossRefPubMed
7.
Miyara M, Yoshioka Y, Kitoh A, Shima T, Wing K, Niwa A, et al. Functional delineation and differentiation dynamics of human CD4+ T cells expressing the FoxP3 transcription factor. Immunity. 2009;30:899–911.CrossRefPubMed
8.
Gogacz M, Winkler I, Bojarska-Junak A, Tabarkiewicz J, Semczuk A, Rechberger T, et al. T regulatory lymphocytes in patients with endometriosis. Mol Med Rep. 2014;10:1072–6.CrossRefPubMed
9.
Olkowska-Truchanowicz J, Bocian K, Maksym RB, Bialoszewska A, Wlodarczyk D, Baranowski W, et al. CD4(+) CD25(+) FOXP3(+) regulatory T cells in peripheral blood and peritoneal fluid of patients with endometriosis. Hum Reprod. 2013;28:119–24.CrossRefPubMed
10.
Takamura M, Koga K, Izumi G, Hirata T, Harada M, Hirota Y, et al. Simultaneous detection and evaluation of four subsets of CD4+ T lymphocyte in lesions and peripheral blood in endometriosis. Am J Reprod Immunol. 2015;74:480–6.CrossRefPubMed
11.
12.
Annes JP, Munger JS, Rifkin DB. Making sense of latent TGFbeta activation. J Cell Sci. 2003;116:217–24.CrossRefPubMed
13.
14.
Ho HN, Wu MY, Yang YS. Peritoneal cellular immunity and endometriosis. Am J Reprod Immunol. 1997;38:400–12.CrossRefPubMed
15.
Dmowski WP, Steele RW, Baker GF. Deficient cellular immunity in endometriosis. Am J Obstet Gynecol. 1981;141:377–83.CrossRefPubMed
16.
American Society for Reproductive Medicine. Revised American Society for Reproductive Medicine classification of endometriosis: 1996. Fertil Steril. 1997;67:817–21.CrossRef
17.
Braundmeier A, Jackson K, Hastings J, Koehler J, Nowak R, Fazleabas A. Induction of endometriosis alters the peripheral and endometrial regulatory T cell population in the non-human primate. Hum Reprod. 2012;27:1712–22.CrossRefPubMedPubMedCentral
18.
Berbic M, Hey-Cunningham AJ, Ng C, Tokushige N, Ganewatta S, Markham R, et al. The role of Foxp3+ regulatory T-cells in endometriosis: a potential controlling mechanism for a complex, chronic immunological condition. Hum Reprod. 2010;25:900–7.CrossRefPubMed
19.
20.
Budiu RA, Diaconu I, Chrissluis R, Dricu A, Edwards RP, Vlad AM. A conditional mouse model for human MUC1-positive endometriosis shows the presence of anti-MUC1 antibodies and Foxp3+ regulatory T cells. Dis Model Mech. 2009;2:593–603.CrossRefPubMed
21.
Tanaka Y, Mori T, Ito F, Koshiba A, Takaoka O, Kataoka H, et al. Exacerbation of endometriosis due to regulatory T cell dysfunction. J Clin Endocrinol Metab. 2017;102:3206–17.CrossRefPubMed
22.
Florek M, Schneidawind D, Pierini A, Baker J, Armstrong R, Pan Y, et al. Freeze and thaw of CD4+CD25+Foxp3+ regulatory T cells results in loss of CD62L expression and a reduced capacity to protect against graft-versus-host disease. PLoS One. 2015;10:e0145763.CrossRefPubMedPubMedCentral
23.
Weiner J, Duran-Struuck R, Zitsman J, Buhler L, Sondermeijer H, McMurchy AN, et al. Restimulation after cryopreservation and thawing preserves the phenotype and function of expanded baboon regulatory T cells. Transplant Direct. 2015;1:1–7.CrossRefPubMed
24.
Dmowski WP. Immunological aspects of endometriosis. Int J Gynaecol Obstet. 1995;50(Suppl 1):S3–S10.CrossRefPubMed
25.
Oral E, Arici A. Pathogenesis of endometriosis. Obstet Gynecol Clin N Am. 1997;24:219–33.CrossRef
26.
27.
Munger JS, Harpel JG, Gleizes PE, Mazzieri R, Nunes I, Rifkin DB. Latent transforming growth factor-beta: structural features and mechanisms of activation. Kidney Int. 1997;51:1376–82.CrossRefPubMed
28.
Todorovic V, Jurukovski V, Chen Y, Fontana L, Dabovic B, Rifkin DB. Latent TGF-beta binding proteins. Int J Biochem Cell Biol. 2005;37:38–41.CrossRefPubMed
29.
Border WA, Noble NA. Transforming growth factor beta in tissue fibrosis. N Engl J Med. 1994;331:1286–92.CrossRefPubMed
30.
De Crescenzo G, Grothe S, Zwaagstra J, Tsang M, O’Connor-McCourt MD. Real-time monitoring of the interactions of transforming growth factor-beta (TGF-beta) isoforms with latency-associated protein and the ectodomains of the TGF-beta type II and III receptors reveals different kinetic models and stoichiometries of binding. J Biol Chem. 2001;276:29632–43.CrossRefPubMed
31.
Walton KL, Makanji Y, Chen J, Wilce MC, Chan KL, Robertson DM, et al. Two distinct regions of latency-associated peptide coordinate stability of the latent transforming growth factor-beta1 complex. J Biol Chem. 2010;285:17029–37.CrossRefPubMedPubMedCentral
32.
Oosterlynck DJ, Meuleman C, Waer M, Koninckx PR. Transforming growth factor-beta activity is increased in peritoneal fluid from women with endometriosis. Obstet Gynecol. 1994;83:287–92.PubMed
33.
Dooley S, Delvoux B, Lahme B, Mangasser-Stephan K, Gressner AM. Modulation of transforming growth factor beta response and signaling during transdifferentiation of rat hepatic stellate cells to myofibroblasts. Hepatology. 2000;31:1094–106.CrossRefPubMed
34.
Zhang Y, McCormick LL, Gilliam AC. Latency-associated peptide prevents skin fibrosis in murine sclerodermatous graft-versus-host disease, a model for human scleroderma. J Invest Dermatol. 2003;121:713–9.CrossRefPubMed
35.
Pizzo A, Salmeri FM, Ardita FV, Sofo V, Tripepi M, Marsico S. Behaviour of cytokine levels in serum and peritoneal fluid of women with endometriosis. Gynecol Obstet Investig. 2002;54:82–7.CrossRef
36.
Rice LM, Padilla CM, McLaughlin SR, Mathes A, Ziemek J, Goummih S, et al. Fresolimumab treatment decreases biomarkers and improves clinical symptoms in systemic sclerosis patients. J Clin Invest. 2015;125:2795–807.CrossRefPubMedPubMedCentral
37.
Lawrence DA. Transforming Growth factor-beta: a general review. Eur Cytokine Netw. 1996;7:363–74.PubMed
38.
Young VJ, Brown JK, Saunders PT, Duncan WC, Horne AW. The peritoneum is both a source and target of TGF-beta in women with endometriosis. PLoS One. 2014;9:e106773.CrossRefPubMedPubMedCentral
39.
40.
Syegh L, Fuleihan Gel-H, Nassar AH. Vitamine D in endometriosis: a causative or confounder factor? Metabolism. 2014;63:32–41.CrossRef
41.
Cuevas M, Cruz ML, Ramirez AE, Flores I, Thompson KJ, Bayona M, et al. Stress during development of experimental endometriosis influence nerve growth and disease progression. Reprod Sci. 2017;1933719117737846 (Epub).
42.
Yuk JS, Shin JS, Shin JY, Oh E, Kim H, Park WI. Nickel allergy is a risk factor for endometriosis: an 11-year population-based nested case-control study. PLoS One. 2015;10:e0139388.CrossRefPubMedPubMedCentral
Metadata
Title
Suppressive regulatory T cells and latent transforming growth factor-β-expressing macrophages are altered in the peritoneal fluid of patients with endometriosis
Authors
Tetsuro Hanada
Shunichiro Tsuji
Misako Nakayama
Shiro Wakinoue
Kyoko Kasahara
Fuminori Kimura
Takahide Mori
Kazumasa Ogasawara
Takashi Murakami
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Reproductive Biology and Endocrinology / Issue 1/2018
Electronic ISSN: 1477-7827
DOI
https://doi.org/10.1186/s12958-018-0325-2

Other articles of this Issue 1/2018

Reproductive Biology and Endocrinology 1/2018 Go to the issue

Short communication

In vitro maturation of oocytes from excised ovarian tissue in a patient with autoimmune ovarian insufficiency possibly associated with Epstein-Barr virus infection

Review

Proteomic profile of human spermatozoa in healthy and asthenozoospermic individuals

Review

Air pollution and female fertility: a systematic review of literature

Research

The dynamic changes in the number of uterine natural killer cells are specific to the eutopic but not to the ectopic endometrium in women and in a baboon model of endometriosis

Research

GnRH dysregulation in polycystic ovarian syndrome (PCOS) is a manifestation of an altered neurotransmitter profile

Research

Cytokines in relation to hCG are significantly altered in asymptomatic women with miscarriage – a pilot study