Altered X-chromosome inactivation in T cells may promote sex-biased autoimmune diseases

When the balance is broken: X-linked gene dosage from two X chromosomes and female-biased autoimmunity

“…Interestingly, we also observed these dispersed patterns of XIST RNA in T cells from pediatric SLE patients in disease remission . Importantly, we found that SLE patient T cells had abnormal overexpression of X‐linked genes and perturbed expression of XIST RNA interactome genes, suggesting that altered expression of these factors might be responsible for the dispersed XIST RNA localization patterns in SLE cells . In sum, abnormal maintenance of XCI appears to be a feature of SLE that explains the frequent observation of overexpressed X‐linked genes.…”

“…Xist RNA localization in circulating NZB/W F1 T cells was also different than in healthy age‐matched controls. Nuclear Xist RNA clusters were detectable in circulating T cells from NZB/W F1 mice at late‐stage disease compared to wild‐type age‐matched samples . Interestingly, we also observed these dispersed patterns of XIST RNA in T cells from pediatric SLE patients in disease remission .…”

“…Nuclear Xist RNA clusters were detectable in circulating T cells from NZB/W F1 mice at late‐stage disease compared to wild‐type age‐matched samples . Interestingly, we also observed these dispersed patterns of XIST RNA in T cells from pediatric SLE patients in disease remission . Importantly, we found that SLE patient T cells had abnormal overexpression of X‐linked genes and perturbed expression of XIST RNA interactome genes, suggesting that altered expression of these factors might be responsible for the dispersed XIST RNA localization patterns in SLE cells .…”

“…). NZB/W F1 in vitro activated splenic CD3+ T cells during the late stage of lupus disease had less Xist RNA clustered at the Xi than healthy age‐matched control females, and had a larger proportion of cells with Xist RNA dispersed throughout the nucleus . Xist RNA localization in circulating NZB/W F1 T cells was also different than in healthy age‐matched controls.…”

“…However, lymphocyte progenitors, which are derived from CLPs, lacked Xist RNA localization at the Xi (Fig. ) . During B cell differentiation, Xist was continuously transcribed yet Xist RNA transcripts were never enriched at the Xi.…”