Increasing evidence supports the anti-inflammatory role of estrogens in Multiple Sclerosis (MS), originating from the observation of reduction in relapse rates among women with MS during pregnancy, but themolecularmechanisms are still not completely understood. Using an integrative data analysis, we identified T helper (Th) 17 and T regulatory (Treg) cell-type-specific regulatory regions (CSR) regulated by estrogen receptor alpha (ERa). These CSRs were validated in polarized Th17 from healthy donors (HD) and in peripheral blood mononuclear cells, Th17 and Treg cells from relapsing remitting (RR) MS patients and HD during pregnancy. 17b-estradiol induces active histone marks enrichment at Forkhead Box P3 (FOXP3)-CSRs and repressive histone marks enrichment at RAR related orphan receptor C (RORC)-CSRs in polarized Th17 cells. A disease-associated epigenetic profile was found in RRMS patients during pregnancy, suggesting a FOXP3 positive regulation and a RORC negative regulation in the third trimester of pregnancy. Altogether, these data indicate that estrogens act as immunomodulatory factors on the epigenomes of CD4+ T cells in RRMS; the identified CSRs may represent potential biomarkers for monitoring disease progression or new potential therapeutic targets.

Pregnancy epigenetic signature in T helper 17 and T regulatory cells in multiple sclerosis

Andrea Iannello;Simona Rolla;MAGLIONE, ALESSANDRO;Giulio Ferrero;Valentina Bardina;Stefania De Mercanti;Francesco Novelli;Simona Cardaropoli;Tullia Todros;Francesca Cordero;Michele De Bortoli;Luca Durelli;Santina Cutrupi
Co-last
;
Marinella Clerico
Co-last
2019

Abstract

Increasing evidence supports the anti-inflammatory role of estrogens in Multiple Sclerosis (MS), originating from the observation of reduction in relapse rates among women with MS during pregnancy, but themolecularmechanisms are still not completely understood. Using an integrative data analysis, we identified T helper (Th) 17 and T regulatory (Treg) cell-type-specific regulatory regions (CSR) regulated by estrogen receptor alpha (ERa). These CSRs were validated in polarized Th17 from healthy donors (HD) and in peripheral blood mononuclear cells, Th17 and Treg cells from relapsing remitting (RR) MS patients and HD during pregnancy. 17b-estradiol induces active histone marks enrichment at Forkhead Box P3 (FOXP3)-CSRs and repressive histone marks enrichment at RAR related orphan receptor C (RORC)-CSRs in polarized Th17 cells. A disease-associated epigenetic profile was found in RRMS patients during pregnancy, suggesting a FOXP3 positive regulation and a RORC negative regulation in the third trimester of pregnancy. Altogether, these data indicate that estrogens act as immunomodulatory factors on the epigenomes of CD4+ T cells in RRMS; the identified CSRs may represent potential biomarkers for monitoring disease progression or new potential therapeutic targets.
01
17
http://dx.doi.org/10.1080/2162402X.2017.1393596
MULTIPLE SCLEROSIS, ESTROGEN RECEPTOR, EPIGENETICS
Andrea Iannello, Simona Rolla, Alessandro Maglione, Giulio Ferrero, Valentina Bardina, Ilenia Inaudi, Stefania De Mercanti, Francesco Novelli, Lucrezia D'Antuono, Simona Cardaropoli, Tullia Todros, Maria Vittoria Turrini, Cinzia Cordioli, Giorgia Puorro, Angela Marsili, Roberta Lanzillo, Vincenzo Brescia Morra, Francesca Cordero, Michele De Bortoli, Luca Durelli, Andrea Visconti, Santina Cutrupi, Marinella Clerico
File in questo prodotto:
File Dimensione Formato  
Ianello2019_PregnancyEpigeneticSignatureMS.pdf

Accesso aperto

Descrizione: Articolo
Tipo di file: PDF EDITORIALE
Dimensione 3.63 MB
Formato Adobe PDF
3.63 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1690070
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 13
  • ???jsp.display-item.citation.isi??? 14
social impact