International Journal of Reproductive BioMedicine

ISSN: 2476-3772

The latest discoveries in all areas of reproduction and reproductive technology.

 

Human Va7.2-Ja33 mucosal-associated invariant T cells in endometrial ectopic tissues tend to produce interferon-gamma: A new player in endometriosis etiology: A case-control study

Published date: May 12 2024

Journal Title: International Journal of Reproductive BioMedicine

Issue title: International Journal of Reproductive BioMedicine (IJRM): Volume 22, Issue No. 3

Pages: 235–244

DOI: 10.18502/ijrm.v22i3.16168

Authors:

Maryam Zare MoghaddamDepartment of Immunology, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.

Fateme ZareReproductive Immunology Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.

Reyhane SandoghsazAbortion Research Center, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.

Abbas KhaliliDepartment of Pediatrics, Shahid Sadoughi Hospital, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.

Ali ShamsAlis743@yahoo.comDepartment of Immunology, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.

Abstract:

Background: Endometriosis is a chronic estrogen-related inflammatory disorder that is known by proliferating endometrial cells in a place outside the uterus. The high presence of immune cells in the peritoneal fluid of women with endometriosis confirms the involvement of the immune system in the pathogenesis of the disease. Mucosal-associated invariant T (MAIT) cells play an undeniable impact on mucosal immunity by the production of interleukin-17, interferon-gamma (IFN-γ), and tumor necrosis factor-alpha. The function of the cells in the pathogenesis of endometriosis is less investigated.

Objective: This study aims to investigate the infiltration of MAIT cells by using the determination levels of Vα7.2-Jα33 gene expression in eutopic and ectopic tissue of endometriosis lesions.

Materials and Methods: In this case-control study, the tested samples include 20 eutopic and 20 ectopic tissues of women with endometriosis and 20 uterine endometrial tissues of women in the control group. Expressions of the Vα-Jα tumor necrosis factor-alpha, interleukin-17A, and IFN-γ genes were analyzed by quantitative reverse transcriptase-polymerase chain reaction.

Results: According to the results, Vα7.2-Jα33 gene expression did not show substantial elevation in the uterine and eutopic endometrial tissues compared to internal gene control as well as in ectopic tissues. Correlation analysis approved a positive relationship between Vα7.2-Jα33 expression genes and IFN-γ levels in ectopic tissues.

Conclusion: Considering the low-expression specific gene of MAIT cells in ectopic tissue, it can be concluded that these cells are present in the endometriotic environment to a certain extent, and there is a possibility of their role in the progression of endometriosis by secreting IFN-γ.

Key words: Endometriosis, MAIT, IFN-γ, TNF-α, TCR V alpha 7.2-J alpha33, IL-17

References:

[1] Koninckx PR, Ussia A, Adamyan L, Wattiez A, Gomel V, Martin DC. Pathogenesis of endometriosis: The genetic/epigenetic theory. Fertil Steril 2019; 111: 327–340.

[2] Parasar P, Ozcan P, Terry KL. Endometriosis: Epidemiology, diagnosis and clinical management. Curr Obstet Gynecol Rep 2017; 6: 34–41.

[3] Parazzini F, Esposito G, Tozzi L, Noli S, Bianchi S. Epidemiology of endometriosis and its comorbidities. Eur J Obstet Gynecol Reprod Biol 2017; 209: 3–7.

[4] Zare Moghaddam M, Ansariniya H, Seifati SM, Zare F, Fesahat F. Immunopathogenesis of endometriosis: An overview of the role of innate and adaptive immune cells and their mediators. Am J Reprod Immunol 2022; 87: e13537.

[5] Classen J, Koschel J, Oehlwein C, Seppi K, Urban P, Winkler C, et al. Nonmotor fluctuations: Phenotypes, pathophysiology, management, and open issues. J Neural Transm 2017; 124: 1029–1036.

[6] Xiao F, Liu X, Guo SW. Platelets and regulatory T cells may induce a type 2 immunity that is conducive to the progression and fibrogenesis of endometriosis. Front Immunol 2020; 11: 610963.

[7] Zhang T, Zhou J, Man GCW, Leung KT, Liang B, Xiao B, et al. MDSCs drive the process of endometriosis by enhancing angiogenesis and are a new potential therapeutic target. Eur J Immunol 2018; 48: 1059–1073.

[8] Legoux F, Salou M, Lantz O. MAIT cell development and functions: The microbial connection. Immunity 2020; 53: 710–723.

[9] Nel I, Bertrand L, Toubal A, Lehuen A. MAIT cells, guardians of skin and mucosa? Mucosal Immunol 2021; 14: 803–814.

[10] Meierovics A, Yankelevich W-JC, Cowley SC. MAIT cells are critical for optimal mucosal immune responses during in vivo pulmonary bacterial infection. Proc Natl Acad Sci 2013; 110: E3119-E3128.

[11] Bister J, Crona Guterstam Y, Strunz B, Dumitrescu B, Haij Bhattarai K, Özenci V, et al. Human endometrial MAIT cells are transiently tissue resident and respond to Neisseria gonorrhoeae. Mucosal Immunol 2021; 14: 357–365.

[12] Gibbs A, Leeansyah E, Introini A, Paquin-Proulx D, Hasselrot K, Andersson E, et al. MAIT cells reside in the female genital mucosa and are biased towards IL-17 and IL-22 production in response to bacterial stimulation. Mucosal Immunol 2017; 10: 35–45.

[13] Xu H, Zhao J, Lu J, Sun X. Ovarian endometrioma infiltrating neutrophils orchestrate immunosuppressive microenvironment. J Ovarian Res 2020; 13: 44.

[14] Li C, Lu Z, Bi K, Wang K, Xu Y, Guo P, et al. CD4+/CD8+ mucosa-associated invariant T cells foster the development of endometriosis: A pilot study. Reprod Biol Endocrinol 2019; 17: 78.

[15] Chiang CM, Hill JA. Localization of T cells, interferongamma and HLA-DR in eutopic and ectopic human endometrium. Gynecol Obstet Invest 1997; 43: 245–250.

[16] Qiu X-M, Lai Z-Z, Ha S-Y, Yang H-L, Liu L-B, Wang Y, et al. IL-2 and IL-27 synergistically promote growth and invasion of endometriotic stromal cells by maintaining the balance of IFN-?? and IL-10 in endometriosis. Reproduction 2020; 159: 251–260.

[17] Zhang Q, Li P, Zhou W, Fang S, Wang J. Participation of increased circulating MAIT cells in lung cancer: A pilot study. J Cancer 2022; 13: 1623–1629.

[18] Fan Q, Nan H, Li Z, Li B, Zhang F, Bi L. New insights into MAIT cells in autoimmune diseases. Biomed Pharmacother 2023; 159: 114250.

[19] Podgaec S, Dias Junior JA, Chapron C, Oliveira RM, Baracat EC, Abrão MS. Th1 and Th2 ummune responses related to pelvic endometriosis. Rev Assoc Med Bras 2010; 56: 92–98.

[20] Yoo J-Y, Jeong J-W, Fazleabas AT, Tayade C, Young SL, Lessey BA. Protein inhibitor of activated STAT3 (PIAS3) is down-regulated in eutopic endometrium of women with endometriosis. Biol Reprod 2016; 95: 11.

[21] Ahn SH, Edwards AK, Singh SS, Young SL, Lessey BA, Tayade C. IL-17A contributes to the pathogenesis of endometriosis by triggering proinflammatory cytokines and angiogenic growth factors. J Immunol 2015; 195: 2591–2600.

[22] Miller JE, Ahn SH, Marks RM, Monsanto SP, Fazleabas AT, Koti M, et al. IL-17A modulates peritoneal macrophage recruitment and M2 polarization in endometriosis. Front Immunol 2020; 11: 108.

[23] Hana T, Terabe M. MAIT cells and MR1 play an immunosuppressive role in glioblastoma through the induction of neutrophils and MDSCs. bioRxiv. 2022:2022.07.17.499189. (Preprint)

[24] He R, Liu X, Zhang J, Wang Z, Wang W, Fu L, et al. NLRC5 inhibits inflammation of secretory phase ectopic endometrial stromal cells by up-regulating autophagy in ovarian endometriosis. Front Pharmacol 2020; 11: 1281.

[25] Odukoya OA, Ajjan R, Lim K, Watson P, Weetman AP, Cooke I. The pattern of cytokine mRNA expression in ovarian endometriosis. Mol Hum Reprod 1997; 3: 393–397.

[26] Koval HD, Chopyak VV, Kamyshnyi OM, Kurpisz MK. Transcription regulatory factor expression in T-helper cell differentiation pathway in eutopic endometrial tissue samples of women with endometriosis associated with infertility. Cent Eur J Immunol 2018; 43: 90–96.

[27] Shi XY, Gu L, Chen J, Guo XR, Shi YL. Downregulation of miR-183 inhibits apoptosis and enhances the invasive potential of endometrial stromal cells in endometriosis. Int J Mol Med 2014; 33: 59–67.

[28] Wu Y, Wu X. [Expression of PROK 1 and its receptor PROKR 1 in endometriosis and its clinical significance]. Zhong Nan Da Xue Xue Bao Yi Xue Ban 2019; 44: 621–627. (in Chinese)

[29] Chae U, Min JY, Kim SH, Ihm HJ, Oh YS, Park SY, et al. Decreased progesterone receptor B/A ratio in endometrial cells by tumor necrosis factor-alpha and peritoneal fluid from patients with endometriosis. Yonsei Med J 2016; 57: 1468–1474.

[30] Kim YA, Kim JY, Kim MR, Hwang KJ, Chang DY, Jeon MK. Tumor necrosis factor-alpha-induced cyclooxygenase-2 overexpression in eutopic endometrium of women with endometriosis by stromal cell culture through nuclear factor-kappaB activation. J Reprod Med 2009; 54: 625– 630.

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