Fig. 10: Proposed mechanism of female-biased SMC1A expression in shaping the inflammatory molecular program of monocytes and predisposition to lupus autoimmunity.

SMC1A, a cohesin complex subunit escaping X-chromosome inactivation, shows enhanced female-biased expression in monocytes from SLE patients as well as in those cultured under lupus-inducing conditions. Under lupus-inducing conditions, SMC1A is redistributed to the active regulatory elements of immune-related genes in monocytes, leading to increased transcriptional levels. Increased SMC1A binding at the enhancers of inflammatory genes, such as IL6 and IL1A, in female than male monocytes during lupus may lead to higher expression levels in the former group. Importantly, SMC1A-regulated genes are upregulated in female monocytes from SLE patients, correlating with a more inflammatory molecular and cytokine fingerprint, as compared to male counterparts. Created in BioRender.