CLTA-4 Expression is Associated with the Maintenance of Chronic Inflammation in Endometriosis and Infertility

Overview

Journal Cells

Publisher MDPI

Specialties Biochemistry
Biophysics
Cell Biology
Molecular Biology

Date 2021 Mar 6

PMID 33668701

Citations 10

Authors

Monika Abramiuk

Dominika Bebnowska

Rafal Hrynkiewicz

Paulina Niedzwiedzka-Rystwej Grzegorz Polak

Jan Kotarski

Jacek Rolinski

Ewelina Grywalska

Affiliations

Soon will be listed here.

Abstract

Altered immune mechanisms are implicated in the pathogenesis of endometriosis. CTLA-4 is a membrane receptor that favors the anergic state of lymphocytes, which may disrupt the immune system response in the endometriotic environment. In this study, we examined the expression of CTLA-4 on T and B cells by flow cytometry and its levels in blood serum and peritoneal fluid by ELISA. Levels of CTLA-4+ T cells were significantly higher in patients with more advanced endometriosis than in those with less advanced disease. Additionally, the negative correlation of CTLA-4 T lymphocytes and the percentage of NK and NKT-like cells in women with endometriosis and infertility may indicate a different etiopathogenesis of endometriosis accompanying infertility. Our findings shed light on the potential of CTLA-4 in developing new diagnostic and therapeutic approaches in endometriosis management.

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References

Blair P, Riley J, Levine B, Lee K, Craighead N, Francomano T . CTLA-4 ligation delivers a unique signal to resting human CD4 T cells that inhibits interleukin-2 secretion but allows Bcl-X(L) induction. J Immunol. 1998; 160(1):12-5. View

Brunner M, Chambers C, Chan F, Hanke J, Winoto A, Allison J . CTLA-4-Mediated inhibition of early events of T cell proliferation. J Immunol. 1999; 162(10):5813-20. View

Chantalat E, Valera M, Vaysse C, Noirrit E, Rusidze M, Weyl A . Estrogen Receptors and Endometriosis. Int J Mol Sci. 2020; 21(8). PMC: 7215544. DOI: 10.3390/ijms21082815. View

Zondervan K, Cardon L, Kennedy S . What makes a good case-control study? Design issues for complex traits such as endometriosis. Hum Reprod. 2002; 17(6):1415-23. DOI: 10.1093/humrep/17.6.1415. View

Giudice L, Kao L . Endometriosis. Lancet. 2004; 364(9447):1789-99. DOI: 10.1016/S0140-6736(04)17403-5. View

Liu Q, Ma P, Liu L, Ma G, Ma J, Liu X . Evaluation of PLGA containing anti-CTLA4 inhibited endometriosis progression by regulating CD4+CD25+Treg cells in peritoneal fluid of mouse endometriosis model. Eur J Pharm Sci. 2016; 96:542-550. DOI: 10.1016/j.ejps.2016.10.031. View

Sillem M, Prifti S, Monga B, Buvari P, Shamia U, RUNNEBAUM B . Soluble urokinase-type plasminogen activator receptor is over-expressed in uterine endometrium from women with endometriosis. Mol Hum Reprod. 1998; 3(12):1101-5. DOI: 10.1093/molehr/3.12.1101. View

Hasson H . Incidence of endometriosis in diagnostic laparoscopy. J Reprod Med. 1976; 16(3):135-8. View

Frydecka I, Daroszewski J, Suwalska K, Zoledziowska M, Tutak A, Slowik M . CTLA-4 (CD152) gene polymorphism at position 49 in exon 1 in Graves' disease in a Polish population of the Lower Silesian region. Arch Immunol Ther Exp (Warsz). 2004; 52(5):369-74. View

10.

Vigano P, Lattuada D, Somigliana E, Abbiati A, Candiani M, Di Blasio A . Variants of the CTLA4 gene that segregate with autoimmune diseases are not associated with endometriosis. Mol Hum Reprod. 2005; 11(10):745-9. DOI: 10.1093/molehr/gah225. View

11.

Shafrir A, Farland L, Shah D, Harris H, Kvaskoff M, Zondervan K . Risk for and consequences of endometriosis: A critical epidemiologic review. Best Pract Res Clin Obstet Gynaecol. 2018; 51:1-15. DOI: 10.1016/j.bpobgyn.2018.06.001. View

12.

Liston W, Bradford W, Downie J, Kerr M . Laparoscopy in a general gynecologic unit. Am J Obstet Gynecol. 1972; 113(5):672-7. DOI: 10.1016/0002-9378(72)90636-9. View

13.

Saverino D, Simone R, Bagnasco M, Pesce G . The soluble CTLA-4 receptor and its role in autoimmune diseases: an update. Auto Immun Highlights. 2015; 1(2):73-81. PMC: 4389044. DOI: 10.1007/s13317-010-0011-7. View

14.

Dunselman G, Vermeulen N, Becker C, Calhaz-Jorge C, DHooghe T, De Bie B . ESHRE guideline: management of women with endometriosis. Hum Reprod. 2014; 29(3):400-12. DOI: 10.1093/humrep/det457. View

15.

Masteller E, Chuang E, Mullen A, Reiner S, Thompson C . Structural analysis of CTLA-4 function in vivo. J Immunol. 2000; 164(10):5319-27. DOI: 10.4049/jimmunol.164.10.5319. View

16.

Sharpe A, Pauken K . The diverse functions of the PD1 inhibitory pathway. Nat Rev Immunol. 2017; 18(3):153-167. DOI: 10.1038/nri.2017.108. View

17.

Schildberg F, Klein S, Freeman G, Sharpe A . Coinhibitory Pathways in the B7-CD28 Ligand-Receptor Family. Immunity. 2016; 44(5):955-72. PMC: 4905708. DOI: 10.1016/j.immuni.2016.05.002. View

18.

Zondervan K, Becker C, Koga K, Missmer S, Taylor R, Vigano P . Endometriosis. Nat Rev Dis Primers. 2018; 4(1):9. DOI: 10.1038/s41572-018-0008-5. View

19.

LINDSTEN T, Lee K, Harris E, Petryniak B, Craighead N, Reynolds P . Characterization of CTLA-4 structure and expression on human T cells. J Immunol. 1993; 151(7):3489-99. View

20.

Ferrero S, Arena E, Morando A, Remorgida V . Prevalence of newly diagnosed endometriosis in women attending the general practitioner. Int J Gynaecol Obstet. 2010; 110(3):203-7. DOI: 10.1016/j.ijgo.2010.03.039. View