HAGEN, S. H.; HENSELING, F.; HENNESEN, J.; SAVEL, Helene; DELAHAYE, Solenne; RICHERT, Laura; ZIEGLER, S. M.; ALTFELD, M.

doi:10.1016/j.celrep.2020.108485

Métadonnées

Afficher la notice complète

Licence d’utilisation du document

Langue

Article de revue

Ce document a été publié dans

Cell Reports. 2020-12-08, vol. 33, n° 10, p. 108485

Résumé en anglais

Immune responses differ between women and men, and type I interferon (IFN) responses following Toll-like receptor 7 (TLR7) stimulation are higher in women. The precise mechanisms driving these sex differences in immunity are unknown. To investigate possible genetic factors, we quantify escape from X chromosome inactivation (XCI) for TLR7 and four other genes (RPS6KA3, CYBB, BTK, and IL13RA1) at the single plasmacytoid dendritic cell (pDC) level. We observe escape from XCI for all investigated genes, leading to biallelic expression patterns. pDCs with biallelic gene expression have significantly higher mRNA levels of the respective genes. Unstimulated pDCs with biallelic TLR7 expression exhibit significantly higher IFNalpha/beta mRNA levels, and IFNalpha exposure results in significantly increased IFNalpha/beta protein production by pDCs. These results identify unanticipated heterogeneity in escape from XCI of several genes in pDCs and highlight the important contribution of X chromosome factors to sex differences in type I IFN responses, which might explain observed sex differences in human diseases.< Réduire

Métadonnées

Partager cette publication !

Licence d’utilisation du document

Heterogeneous Escape from X Chromosome Inactivation Results in Sex Differences in Type I IFN Responses at the Single Human pDC Level

Langue

Ce document a été publié dans

Résumé en anglais

URI

DOI

Unités de recherche