Profile of TNF-alpha receptors expressed in Th17 CD4+ lymphocytes in the peripheral blood of pregnant women with preeclampsia

• Grant number: 21/12564-2
• Support Opportunities: Scholarships in Brazil - Master
• Effective date (Start): March 01, 2022
• Effective date (End): July 31, 2023
• Field of knowledge: Health Sciences - Medicine - Maternal and Child Health
• Principal Investigator: Maria Terezinha Serrão Peraçoli
• Grantee: Patrícia Braga da Silva
• Host Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Associated scholarship(s): 22/11362-0 - Effect of progesterone on jurkat cells stimulated with plasma of pregnant women with preeclampsia, BE.EP.MS

Abstract

Pregnant women with preeclampsia (PE) present a shift in the immune response to an inflammatory profile, resulting from the endogenous activation of innate and adaptive immunity cells. The activation of peripheral blood monocytes, with exacerbated production of inflammatory cytokines such as TNF-± and other inflammatory mediators, can cause activation of adaptive immune cells, generating inflammatory CD4+ T cells and a decrease in the production of anti-inflammatory cytokines. TNF-± can exert different functional effects on CD4+ T lymphocyte subpopulations through interaction with TNFR1 and TNFR2 receptors. The binding of TNF-± to these two receptors activates different signaling pathways. TNFR1 induces cell death by apoptosis or necrosis and is also important for the development of inflammatory effector T cells, whereas TNFR2 is preferentially expressed by regulatory T cells (Treg). It is already known that in PE, the T lymphocyte response is shifted to an inflammatory Th1 and Th17 profile in detriment to a regulatory profile, and this balance between Treg and Th17 cells may be critical for tolerance to the fetus and for disease prevention. This project aims to determine the expression of tumor necrosis factor-± receptors (TNFR1 and TNFR2) in peripheral blood CD4+ Th17 cells and its association with plasma levels of TNF-± and the soluble form of these receptors in pregnant women with PE. Forty pregnant women will be evaluated, 20 with PE and 20 normotensive pregnant women, matched for gestational age. The blood collected from these pregnant women will be centrifuged, the plasma separated and stored at -80°C for TNFR1 and TNFR2 soluble receptors, and TNF-± measurement by ELISA. The percentage of CD4+ Th17 cells will be determined by the expression of the transcription factor ROR³t, the expression of TNF-± receptors (TNFR1 and TNFR2) in this subpopulation, and the intracytoplasmic expression of IL-17A by flow cytometry, using specific monoclonal antibodies, labeled with fluorochromes soon after blood collection (endogenous expression). The results will be analyzed using parametric or non-parametric tests with a significance level of 5%. (AU)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

SILVA, Patrícia Braga da. Profile of TNF-α receptors expressed in Th17 CD4+ lymphocytes in the peripheral blood of pregnant women with preeclampsia. 2023. Master's Dissertation - Universidade Estadual Paulista (Unesp). Faculdade de Medicina. Botucatu Botucatu.