title: Pregnancy level of estrogen attenuates experimental autoimmune encephalomyelitis in both ovariectomized and pregnant C57BL/6 mice through expansion of Treg and Th2 cells.
abstract: Pregnancy suppressive effect on autoimmune diseases including Multiple Sclerosis and Rheumatoid Arthritis may result from high levels of sex steroids such as estrogen and estriol. This study was designed to reveal the molecular and cellular mechanisms underlying the effect of estrogen on MS alleviation. Female C57BL/6 mice were immunized with MOG35-55. Clinical scores and other relevant parameters were monitored daily. Brain and spinal cord histology was performed to measure lymphocyte infiltration and central nervous system demyelination. Th1/Th2/Th17 and Treg cell profiles were determined through ELISA, flow cytometry, and real-time PCR. Transcription factor expression levels in the CNS were assessed by real-time PCR and T cell differentiation was explored through flow cytometry examination. Pregnancy and pregnancy level of estrogen alleviated clinical manifestations in EAE induced mice, reduced CNS demyelination and cell infiltration, suppressed spleen T cell proliferation, enhanced production of anti-inflammatory cytokines in splenocytes and increased the percentage of Th2 and Treg cells. Furthermore, the results of real-time PCR for transcription factors and related cytokines of Th1/Th2/Th17 and Treg cells in CNS showed reduced expression levels of Th1 and Th17 transcription factors, including T-bet and ROR-γt, and decreased Th1 and Th17 cytokines including IFN-γ, TNF-α, IL-17 and IL-23. These results are the first to indicate that pregnancy and pregnancy level of estrogen ameliorate the EAE condition by favoring Treg and Th2 differentiation through induced expression of Foxp3 and GATA3 in the CNS. Moreover, pregnancy and pregnancy level of estrogen decreased mRNA levels of T-bet and ROR-γt in the CNS.
authors.affiliation: Immunology Research Center, BuAli Research Institute, Department of Immunology and Allergy, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Dariush
authors.initials: D
authors.lastname: Haghmorad
authors.affiliation: Inflammation and Inflammatory Diseases Research Center, Department of Immunology and Allergy, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Abbas Ali
authors.initials: AA
authors.lastname: Amini
authors.affiliation: Department of Genetics, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
authors.forename: Mohammad Bagher
authors.initials: MB
authors.lastname: Mahmoudi
authors.affiliation: Immunology Research Center, BuAli Research Institute, Department of Immunology and Allergy, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Rastin
authors.affiliation: Neurocognitive Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Hosseini
authors.affiliation: Immunology Research Center, BuAli Research Institute, Department of Immunology and Allergy, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: Mahmoudim@mums.ac.ir.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Mahmoudi
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D001973:Bromodeoxyuridine / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004660:Encephalitis / Q000139:chemically induced / Q000188:drug therapy; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy*; D004967:Estrogens / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D010052:Ovariectomy; D011247:Pregnancy; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology; D013997:Time Factors
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D004967:Estrogens; D001973:Bromodeoxyuridine
keywords: Central nervous system; Estrogen; Multiple sclerosis; Pregnancy