Regulatory T cells activation in deep endometriosis

• Grant number: 14/08227-7
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: December 01, 2014
• End date: November 30, 2016
• Field of knowledge: Health Sciences - Medicine - Maternal and Child Health
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Sérgio Podgaec
• Grantee: Bárbara Yasmin Gueuvoghlanian Silva Lopes
• Host Institution: Instituto Israelita de Ensino e Pesquisa Albert Einstein (IIEPAE). Sociedade Beneficente Israelita Brasileira Albert Einstein (SBIBAE). São Paulo , SP, Brazil

Abstract

Endometriosis is characterized by the presence of endometrial tissue outside the uterine cavity and affects about 10% of the world's women population in reproductive age. Its pathophysiology remains unclear but the most currently accepted mechanism is the retrograde menstruation. The intriguing question that remains unsolved is the fact that most women suffer retrograde menstruation, but only a portion develops endometriosis. Thus, the current theory is that these women present immunological changes that favor the endometrium implantation in extra uterine environment. In fact, alterations in the expression of some cytokines and immune cells in peripheral blood and peritoneal fluid have been described in women with endometriosis. However, the evaluation of the presence of T cells and their subtypes in this disease is still very preliminary. Some studies indicate that the presence of regulatory T cells (Treg) in the peritoneal fluid is higher in these women, which could indicate an anti- inflammatory environment, making the environment more propitious to adhesion and proliferation of these cells. Nevertheless, it has not been analyzed if these Treg cells are actually active and exercising a favorable support to endometrial foci implantation. To this end, this study aims to evaluate in Treg cells (CD4+CD25+CD127dim/-FOXP3+) of healthy women and women with deep endometriosis the activation cell surface markers CD45RA, CD45RO, TNFRII, CD25, HLA-DR, CD127, GITR, CTLA-4 and ICOS in the peripheral blood and peritoneal fluid by flow cytometry technique. In addition, we will also assess IL-10, TGFB, TNFA and IL-6 mRNA expression, in order to observe whether these cells are actually producing cytokines that may interfere in immune response. For this, Treg cells (CD4+CD25+CD127dim/-) from peripheral blood and peritoneal fluid of the same patient will be separated by magnetic microbeads, and subsequently total RNA will be extracted. Then, it will be performed the reverse transcription and the analysis of mRNA expression of selected cytokines, Foxp3 and GAPDH and beta-actin (normalizing genes), with primers of TaqMan methodology. (AU)

Scientific publications

(4)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

HERNANDES, CAMILA; GUEUVOGHLANIAN-SILVA, BARBARA YASMIN; MONNAKA, VITOR ULISSES; RIBEIRO, NATALIA MAZINI; PEREIRA, WELBERT DE OLIVEIRA; PODGAEC, SERGIO. Regulatory T cells isolated from endometriotic peritoneal fluid express a different number of Toll-like receptors. Einstein (São Paulo), v. 18, 2020. (14/08227-7, 13/27092-2)

GUEUVOGHLANIAN-SILVA, BARBARA YASMIN; HERNANDES, CAMILA; CORREIA, RODOLFO PATUSSI; PODGAEC, SERGIO. Deep Infiltrating Endometriosis and Activation and Memory Surface Markers and Cytokine Expression in Isolated Treg Cells. REPRODUCTIVE SCIENCES, v. 27, n. 2, p. 599-610, FEB 2020. (14/08227-7, 13/27092-2)

LEITE DE BARROS, ISABELA BOTTURA; MALVEZZI, HELENA; GUEUVOGHLANIAN-SILVA, BARBARA YASMIN; PICCINATO, CARLA AZEVEDO; RIZZO, LUIZ VICENTE; PODGAEC, SERGIO. What do we know about regulatory T cells and endometriosis? A systematic review. JOURNAL OF REPRODUCTIVE IMMUNOLOGY, v. 120, p. 48-55, APR 2017. (13/27092-2, 14/08227-7)

HERNANDES, CAMILA; GUEUVOGHLANIAN-SILVA, BARBARA YASMIN; MONNAKA, VITOR ULISSES; RIBEIRO, NATALIA MAZINI; PEREIRA, WELBERT DE OLIVEIRA; PODGAEC, SERGIO. Regulatory T cells isolated from endometriotic peritoneal fluid express a different number of Toll-like receptors. Einstein (São Paulo), v. 18, p. 6-pg., 2020-01-01. (14/08227-7, 13/27092-2)