X chromosome in autoimmunity

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The X chromosome plays a significant role in autoimmunity, and this is believed to contribute to the higher prevalence of autoimmune diseases in females compared to males. The X chromosome contains a large number of immune-related genes, which can influence the immune response10. In females, one of the two X chromosomes is typically inactivated during embryogenesis to equalize the dosage of X-linked genes between males and females, a process known as X chromosome inactivation (XCI)12. However, some genes can escape this inactivation, leading to a higher expression of these genes in females112. This escape from XCI is thought to contribute to the enhanced susceptibility to autoimmune diseases in females14. Moreover, skewed X chromosome inactivation, where one X chromosome is preferentially inactivated in a significant proportion of cells, or reactivation of parts of the inactive X chromosome, can lead to an imbalance in the expression of X-linked genes, which may contribute to the development of autoimmunity4. Specific genes on the X chromosome have been implicated in autoimmunity. For instance, the Kdm6a gene, which is expressed more in women's immune cells than in men's, has been associated with a heightened susceptibility to autoimmune diseases7. Furthermore, a recent study suggested that a special set of molecules acting on the extra X chromosome carried by women might contribute to the higher incidence of autoimmune diseases in women2. In conclusion, the X chromosome, through various mechanisms such as escape from XCI, skewed XCI, and the presence of specific immune-related genes, plays a crucial role in autoimmunity and the sex bias observed in autoimmune diseases.
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