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Immunomodulatory effect of Vitamin D on CD4+ t cell subsets in pregnant women with preeclampsia

Grant number: 16/23450-0
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): April 01, 2018
Effective date (End): February 29, 2020
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Maria Terezinha Serrão Peraçoli
Grantee:Vanessa Rocha Ribeiro
Home Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Studies suggest that preeclampsia (PE) is characterized by abnormal activation of the innate and adaptive immune systems. Regulatory T (Treg) cells are a population of T cells responsible for maintenance of tolerance and for the control of inflammation, while Th17 cells mediate various types of inflammatory reactions, having opposite actions to Treg cells. The occurrence of a systemic inflammatory response in PE seems to be due to an imbalance of CD4 + T cell subpopulations caused by increased in Th17 cell number and decrease in regulatory T cells compared to normotensive pregnant women. Therefore, the balance between Treg and Th17 cells may be critical for tolerance to the fetus and to prevent PE. The present study aims to evaluate the in vitro modulatory effect of vitamin D A on peripheral blood mononuclear cells (PBMC) of preeclamptic pregnant women, with emphasis on subpopulations of CD4+ Th17 and regulatory T cells. There will be studied 20 pregnant women with PE and 20 normotensive, matched by gestational age. Peripheral blood is obtained from pregnant women from both groups for determination of plasma concentrations of vitamin D [25(OH)D] and vitamin D receptor. The modulatory effect of vitamin D on CD4+ T cell subsets (Th1, Th2, Th17 and Treg) wil be evaluated by the expression of the transcription activators for Th1 (STAT4), Th2 (STAT6), Th17 (STAT3) and Treg (STAT5) and by expression of intracytoplasmic transcription factors for Th1 (T-bet), Th2 (GATA-3), Th17 (ROR³t and Runx1) and Treg (FoxP3) that are characteristics of each T cell subset employing flow cytometry and RT-qPCR. The profile of pro- and anti-inflammatory cytokines IFN-³ , TNF-±, IL-4, IL-6, IL-17, IL-22, IL-10, TGF-² and IL-23 receptor after treatment or not with vitamin D will be evaluate in the supernatant of peripheral blood mononuclear cell cultures from preeclamptic and normotensive pregnant women by CBA (flow cytometry) and ELISA.