MODULATORY EFFECT OF PROGESTERONE, PIBF, AND MAGNESIUM SULFATE ON IMMUNE CHECKPOINTS AND TNFR2 EXPRESSION BY MoT AND THP-1 CELLS

• Grant number: 25/15686-2
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: January 14, 2026
• End date: January 13, 2027
• Field of knowledge: Health Sciences - Medicine - Maternal and Child Health
• Principal Investigator: Maria Terezinha Serrão Peraçoli
• Grantee: Patrícia Braga da Silva
• Supervisor: Lorena Machado Amaral
• Host Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Institution abroad: University of Mississippi Medical Center (UMMC), United States
• Associated to the scholarship: 23/17023-5 - EXPRESSION OF ANTI-INFLAMMATORY BIOMARKERS BY PERIPHERAL BLOOD REGULATORY T CELLS IN PREGNANT WOMEN WITH PRE-ECLAMPSIA, BP.DR

Abstract

Preeclampsia (PE) is a syndrome specific to human pregnancy, characterized by an intense systemic inflammatory response, mediated by monocytes activation, as well as by imbalance between lymphocyte subpopulations, which is critical for fetal tolerance and disease prevention. The activation of innate and adaptive immune cells, with exacerbated production of cytokines and differences in the expression of TNF receptors in T cells, may be responsible for the Th17/Treg imbalance. Molecules called immune checkpoints, or biomolecules with negative regulatory activity, are expressed mainly in Treg cells and are considered responsible for the balance between pro and anti-inflammatory signals, which occur at the maternal-fetal interface to ensure maternal tolerance and successful pregnancy. Furthermore, the differentiated expression of these immune biomarkers in Tregs may reflect changes in the function and proliferation capacity of these cells, as well as these changes may occur due to a failure in the modulation mechanisms capable of regulating inflammation, which may cause maladaptation of the immune response, resulting in the manifestation of PE. The present project aims to evaluate whether treatment with progesterone, PIBF, and magnesium sulfate modulate the expression of immune checkpoints, mTNF and TNFR2 by MoT and THP-1 cells stimulated with TNF-¿ and plasma from preeclamptic women. The MoT and THP-1 cell lines will be cultured and then incubated in a medium containing 20% (v/v) plasma from PE or NT pregnant women and treated with progesterone, PIBF and magnesium sulfate. Cells and supernatant will be used to perform the assays. The gene expression of immune checkpoints, TNF-¿, IL-10, TNFR2 and FoxP3 will be evaluated by RT-qPCR. The expression of immune checkpoints, mTNF and TNFR2 will be evaluated by flow cytometry. The concentration of soluble form of TNFR2, as well as the cytokines TNF-¿ and IL-10 in the cultured supernatant of MoT and THP-1 cells will be determine by ELISA. The results will be analyzed using parametric or non-parametric tests with a significance level of 5%. (AU)