CLINICAL IMMUNOLOGY
Transcription regulatory factor expression in T-helper cell differentiation pathway in eutopic endometrial tissue samples of women with endometriosis associated with infertility
Submission date: 2016-07-14
Final revision date: 2017-01-03
Acceptance date: 2017-01-03
Publication date: 2018-03-30
Cent Eur J Immunol 2018;43(1):90-96
KEYWORDS
ABSTRACT
Endometriosis is a disease of epidemiological gravity of unknown primary reason. A complex of constitutional factors including the immune system has been considered as its background.
The aim of the study was to identify Th1 and Th2 cells as well as the T-regulatory subset in the endometrium of women with endometriosis associated with infertility upon transcription factors expression. Expression of T-bet, GATA3, and Foxp3 genes was examined using a method of polymerase chain reaction (PCR) in the eutopic endometrial samples of 20 women with endometriosis associated with infertility and 20 women with infertility of tubal origin. An increase in mRNA expression for T-bet and GATA3 with prevailing mRNA level for T-bet and a decrease in Foxp3 expression were observed. In conclusion, the revealed changes in expression of transcription factors may indicate the imbalance between T-helper cells of the Th1 and Th2 type and elimination of regulatory function of T-cells, which can be one of the causes of endometriosis predisposing to the development of infertility associated with this disease.
The aim of the study was to identify Th1 and Th2 cells as well as the T-regulatory subset in the endometrium of women with endometriosis associated with infertility upon transcription factors expression. Expression of T-bet, GATA3, and Foxp3 genes was examined using a method of polymerase chain reaction (PCR) in the eutopic endometrial samples of 20 women with endometriosis associated with infertility and 20 women with infertility of tubal origin. An increase in mRNA expression for T-bet and GATA3 with prevailing mRNA level for T-bet and a decrease in Foxp3 expression were observed. In conclusion, the revealed changes in expression of transcription factors may indicate the imbalance between T-helper cells of the Th1 and Th2 type and elimination of regulatory function of T-cells, which can be one of the causes of endometriosis predisposing to the development of infertility associated with this disease.
REFERENCES (52)
1.
Baskakov VP, Cvelev JV, Kira EF (2002): Jendometrioidnaja bolezn’ Endometrioidnaya bol’ezn. Izdatel’stvo N-L 452: 13.
2.
Cramer DW, Missmer SA (2002): The epidemiology of endometriosis. Ann N Y Acad Sci 955: 11-22.
3.
McLeod BS, Retzloff MG (2010): Epidemiology of endometriosis: an assessment of risk factors. Clin Obstet Gynecol 53: 389-396.
5.
Allaire C (2006): Endometriosis and infertility: a review. J Reprod Med 51: 164-168.
6.
Juz’ko OM, Prijmak SG, Prijmak IA, Begal’ LV (2005): Rehabilitation of reproductive function of women with infertility in endometriosis after laparoscopic surgery. Shpital’na hirurgija 2: 94-98.
7.
Savickij GA, Gorbushin SM (2002): Peritoneal endometriosis and infertility (clinical and morphological studies). JeLBISPb: 170.
8.
Burney RO, Giudice LC (2012): Pathogenesis and pathophysiology of endometriosis. Fertil Steril 98: 511-519.
9.
Vinatier D, Orazi G, Cosson M, et al. (2001): Theories of endometriosis. Eur J Obstet Gynecol Reprod Biol 96: 21-34.
10.
Acién P, Velasco I (2013): Endometriosis: a disease that remains enigmatic. ISRN Obstet Gynecol 2013: 242149.
11.
Kyama CM, Debrock S, Mwenda JM, et al. (2003): Potential involvement of the immune system in the development of endometriosis. Reprod Biol Endocrinol 1: 123.
12.
Richter ON, Dorn C, Rösing B, et al. (2005): Tumor necrosis factor alpha secretion by peritoneal macrophages in patients with endometriosis. Arch Gynecol Obstet 271: 143-147.
13.
Koninckx PR, Craessaerts M, Timmerman D, et al. (2008): Anti-TNF-αlpha treatment for deep endometriosis-associated pain: a randomized placebo-controlled trial. Hum Reprod 23: 2017-2023.
14.
Somigliana E, Viganò P, Rossi G, et al. (1999): Endometrial ability to implant in ectopic sites can be prevented by interleukin-12 in a murine model of endometriosis. Hum Reprod 14: 2944-2950.
15.
Itoh H, Sashihara T, Hosono A, et al. (2011): Interleukin-12 inhibits development of ectopic endometriotic tissues in peritoneal cavity via activation of NK cells in a murine endometriosis model. Cytotechnology 63: 133-141.
16.
Ou Yang Z, Hirota Y, Osuga Y, et al. (2008): Interleukin-4 stimulates proliferation of endometriotic stromal cells. Am J Pathol 173: 463-469.
17.
Sinaii N, Cleary SD, Ballweg ML, et al. (2002): High rates of autoimmune and endocrine disorders, fibromyalgia, chronic fatigue syndrome and atopic diseases among women with endometriosis: a survey analysis. Hum Reprod 17: 2715-2724.
18.
Coomes SM, Pelly VS, Wilson MS (2013): Plasticity within the +CD4+ T-cell lineage: when, how and what for? Open Biol 3: 120157.
19.
Yang XO, Nurieva R, Martinez GJ, et al. (2008): Molecular antagonism and plasticity of regulatory and inflammatory T cell programs. Immunity 29: 44-56.
20.
Wong WF, Kohu K, Chiba T, et al. (2011): Interplay of transcription factors in T-cell differentiation and function: the role of Runx. Immunology 132: 157-164.
21.
Dong C (2008): TH17 cells in development: an updated view of their molecular identity and genetic programming. Nat Rev Immunol 8: 337-348.
22.
Naito T, Tanaka H, Naoe Y, et al. (2011): Transcriptional control of T-cell development. Int Immunol 23: 661-668.
23.
Evans CM, Jenner RG (2013): Transcription factor interplay in T helper cell differentiation. Brief Funct Genomics 12: 499-511.
24.
Murphy KM, Reiner SL (2002): The lineage decisions of helper T cells. Nat Rev Immunol 2: 933-944.
25.
Kemp KL, Levin SD, Bryce PJ, et al. (2010): Lck mediates Th2 differentiation through effects on T-bet and GATA-3. J Immunol 184: 4178-4184.
26.
Usui T, Nishikomori R, Kitani A, et al. (2003): GATA-3 suppresses Th1 development by downregulation of Stat4 and not through effects on IL-12Rbeta2 chain or T-bet. Immunity 18: 415-428.
27.
Ouyang W, Löhning M, Gao Z, et al. (2000): Stat6-independent GATA-3 autoactivation directs IL-4-independent Th2 development and commitment. Immunity 12: 27-37.
28.
Fontenot JD, Rasmussen JP, Williams LM, et al. (2005): Regulatory T cell lineage specification by the forkhead transcription factor foxp3. Immunity 22: 329-341.
29.
Ivanov II, McKenzie BS, Zhou L, et al. (2006): The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell 126: 1121-1133.
30.
Ichiyama K, Yoshida H, Wakabayashi Y, et al. (2008): Foxp3 inhibits RORgammat-mediated IL-17A mRNA transcription through direct interaction with RORgammat. J Biol Chem 283: 17003-17008.
31.
Skapenko A, Leipe J, Niesner U, et al. (2004): GATA-3 in human T cell helper type 2 development. J Exp Med 199: 423-248.
32.
Chakir H, Wang H, Lefebvre DE, et al. (2003): T-bet/GATA-3 ratio as a measure of the Th1/Th2 cytokine profile in mixed cell populations: predominant role of GATA-3. J Immunol Methods 2278: 157-169.
33.
Li X, Sun Q, Zhang M, Chen J, Liu Z (2013): The diagnostic value of transcription factors T-bet/GATA3 ratio in predicting antibody-mediated rejection. Clin Dev Immunol 2013: 460316.
34.
Kanwar B, Favre D, McCune JM (2010): Th17 and regulatory T cells: implications for AIDS pathogenesis. Curr Opin HIV AIDS 5: 151-157.
35.
Lin ZW, Wu LX, Xie Y, et al. (2015): The expression levels of transcription factors T-bet, GATA-3, RORt and FOXP3 in peripheral blood lymphocyte (PBL) of patients with liver cancer and their significance. Int J Med Sci 12: 7-16.
36.
Saito S, Nakashima A, Shima T, et al. (2010): Th1/Th2/Th17 and regulatory T-cell paradigm in pregnancy. Am J Reprod Immunol 63: 601-610.
37.
Chaouat G (2007): The Th1/Th2 paradigm: still important in pregnancy? Semin Immunopathol 29: 95-113.
38.
Chen P, Zhang Z, Chen Q, et al. (2012): Expression of Th1 and Th2 cytokine-associated transcription factors, T-bet and GATA-3, in the eutopic endometrium of women with endometriosis. Acta Histochem 114: 779-784.
39.
Szabo SJ, Sullivan BM, Peng SL, et al. (2003): Molecular mechanisms regulating Th1 immune responses. Annu Rev Immunol 21: 713-758.
40.
Szabo SJ, Kim ST, Costa GL, et al (2000): A novel transcription factor, T-bet, directs Th1 lineage commitment. Cell 100: 655-669.
41.
Afkarian M, Sedy JR, Yang J, et al. (2002): T-bet is a STAT1- induced regulator of IL-12R expression in naïve CD4+ T cells. Nat Immunol 3: 549-557.
42.
Usui TJC, Preiss Y, Kanno ZJ, et al. (2006): T-bet regulates Th1 responses through essential effects on GATA-3 function rather than on IFNG gene acetylation and transcription. J Exp Med 203: 755-766.
43.
Fairbanks F, Abrão MS, Podgaec S, et al. (2009): Interleukin-12 but not interleukin-18 is associated with severe endometriosis. Fertil Steril 91: 320-324.
44.
Koval HD, Pashkovskaja NV, Olenovich OA, et al. (2013): Peculiarities of Systemic and Local Production of Anti-inflammatory Cytokines in Women with Endometriosis Associated with Infertility. Collected papers of the International Scientific Conference “Modern Studies of Medical-Biological Sciences: Improvement of Diagnostics, Elaboration of Preventive Measures and Therapy of Diseases”. Russia, Kirov, June 26-28: 67-73.
45.
André GM, Barbosa CP, Teles JS, et al. (2011): Analysis of FOXP3 polymorphisms in infertile women with and without endometriosis. Fertil Steril 95: 2223-2227.
46.
Chen S, Zhang J, Huang C, et al. (2012): Expression of the T regulatory cell transcription factor FoxP3 in peri-implantation phase endometrium in infertile women with endometriosis. Reprod Biol Endocrinol 10: 34.
47.
Mor G, Cardenas I, Abrahams V, et al. (2011): Inflammation and pregnancy: the role of the immune system at the implantation site. Ann N Y Acad Sci 1221: 80-87.
48.
Tilburgs T, Claas FH, Scherjon SA (2010): Elsevier trophoblast research award lecture: unique properties of decidual T cells and their role in immune regulation during human pregnancy. Placenta 31: 82-86.
49.
Berbic M, Hey-Cunningham AJ, Ng C, et al. (2010): The role of Foxp3+ regulatory T-cells in endometriosis: a potential controlling mechanism for a complex, chronic immunological conditio. Hum Reprod 25: 900-907.
50.
Matarese G, De Placido G, Nikas Y, et al. (2003): Pathogenesis of endometriosis: natural immunity dysfunction or autoimmune disease? Trends Mol Med 9: 223-228.
51.
Teles A, Schumacher A, Kühnle MC, et al. (2013): Control of Uterine Microenvironment by Foxp3+ Cells Facilitates Embryo Implantation Front Immunol 4: 1-12.
52.
Jasper MJ, Tremellen KP, Robertson SA (2006): Primary unexplained infertility is associated with reduced expression of the T-regulatory cell transcription factor Foxp3 in endometrial tissue. Mol Hum Reprod 12: 301-308.
Share
RELATED ARTICLE
| eISSN: | 1644-4124 |
| ISSN: | 1426-3912 |
We process personal data collected when visiting the website. The function of obtaining information about users and their behavior is carried out by voluntarily entered information in forms and saving cookies in end devices. Data, including cookies, are used to provide services, improve the user experience and to analyze the traffic in accordance with the Privacy policy. Data are also collected and processed by Google Analytics tool (more).
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
