Cristian Roberto Falcón1, Fernando F Martínez, Franco Carranza, Laura Cervi, Claudia C Motrán. 1. Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Haya de la Torre y Medina Allende, Ciudad Universitaria, Córdoba, Argentina.
Abstract
PROBLEM: The contribution of Pregnancy-specific glycoproteins (PSG), the major variant of PSG released into the circulation during pregnancy, to the pregnancy-dependent improvement of rheumatoid arthritis (RA) has still not been elucidated. METHOD OF STUDY: Collagen-induced arthritis (CIA) was used to test the hypothesis that PSG1a when released into circulation has a modulatory role on the Th1-pathogenic response, thus improving the CIA symptoms. In vivo expression of PSG1a was induced by injection of the vaccinia (Vac)-based expression vector harboring the complete open-reading frame of PSG1a cDNA. RESULTS: In vivo PSG1a expression during the induction of CIA ameliorated the clinical symptoms, thereby reducing the arthritis score and incidence. Significantly lower levels of IL-17, IL-6, and IFN-γ, but higher levels of TGF-β and IL-10 were secreted by collagen type II-stimulated spleen mononuclear cells from Vac-PSG1a-treated mice compared with control mice. Moreover, Vac-PSG1a treatment promoted the increase in splenic CD4+CD25+Foxp3+ Treg cells. CONCLUSION: Pre-clinical Vac-PSG1a treatment suppressed the Th1- and Th17-type-specific responses, leading to an increase in splenic Treg cells as well as IL-10- and TGF-β-secreting cells, with the CIA symptoms being ameliorated.
PROBLEM: The contribution of Pregnancy-specific glycoproteins (PSG), the major variant of PSG released into the circulation during pregnancy, to the pregnancy-dependent improvement of rheumatoid arthritis (RA) has still not been elucidated. METHOD OF STUDY: Collagen-induced arthritis (CIA) was used to test the hypothesis that PSG1a when released into circulation has a modulatory role on the Th1-pathogenic response, thus improving the CIA symptoms. In vivo expression of PSG1a was induced by injection of the vaccinia (Vac)-based expression vector harboring the complete open-reading frame of PSG1a cDNA. RESULTS: In vivo PSG1a expression during the induction of CIA ameliorated the clinical symptoms, thereby reducing the arthritis score and incidence. Significantly lower levels of IL-17, IL-6, and IFN-γ, but higher levels of TGF-β and IL-10 were secreted by collagen type II-stimulated spleen mononuclear cells from Vac-PSG1a-treated mice compared with control mice. Moreover, Vac-PSG1a treatment promoted the increase in splenic CD4+CD25+Foxp3+ Treg cells. CONCLUSION: Pre-clinical Vac-PSG1a treatment suppressed the Th1- and Th17-type-specific responses, leading to an increase in splenic Treg cells as well as IL-10- and TGF-β-secreting cells, with the CIA symptoms being ameliorated.
Authors: Kyle Malone; Jennifer A Shearer; John M Williams; Anne C Moore; Tom Moore; Christian Waeber Journal: Brain Behav Immun Health Date: 2022-08-24
Authors: Karlie Jones; Angela Ballesteros; Margaret Mentink-Kane; James Warren; Shemona Rattila; Harry Malech; Elizabeth Kang; Gabriela Dveksler Journal: PLoS One Date: 2016-07-07 Impact factor: 3.240