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The X chromosome in immune functions: when a chromosome makes the difference
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Journal Article
The X chromosome in immune functions: when a chromosome makes the difference
2010
Overview
Key Points
Females are more immunoreactive than males and, although sex hormones have an important role in immune functions, the X chromosome is fundamental in shaping sex-specific immune responses.
X-linked specific diseases usually affect only males, simply because they are hemizygous for X chromosome alleles. The fact that females carry two X chromosomes, and therefore two different allelic options to be used by cells, means that they have two possible physiological responses.
Mosaicism, caused by X chromosome inactivation, is one mechanism by which females can have an immune advantage over males, but there are also other features associated with the X chromosome that can modulate differences between female and male immune responses and even lead to immunological differences between individual females.
Although X chromosome inactivation is expected to balance the levels of female and male gene expression, several genes located in the non-recombining regions of the sex chromosomes can escape inactivation, and females may have elevated gene expression of these genes. Moreover, females may present extreme skewing of X chromosome inactivation and show overrepresentation of one of the parental X chromosomes.
Escape from X chromosome silencing and X inactivation skewing may account for immune differences between the sexes. These mechanisms may be involved in the development of autoimmunity, as skewed X chromosome inactivation or reactivation of parts of the inactive X chromosome can lead to the breakdown of self tolerance.
The number of X-linked genes and microRNAs with an identified role in immunity is increasing, and it is possible that naturally occurring variations in these genes and microRNAs account for immunological differences between genders.
This Review describes the mechanisms by which the X chromosome regulates immune responses. The authors discuss how the effects of this chromosome can account for many of the immunological differences, such as altered susceptibility to infection or autoimmune disease, that occur between the sexes.
In response to various immune challenges, females show better survival than males; the X chromosome has an important role in this immunological advantage. X chromosome-linked diseases are usually restricted to males, who have only one copy of the X chromosome; however, females are more prone to autoimmune diseases, and the X chromosome may be involved in the breakdown of self tolerance. Several hypotheses have been proposed in recent years that support a role for the X chromosome in shaping autoimmune responses. Here, we review the main mechanisms responsible for increased immune activity in females. This provides a survival advantage in the face of pathogenic insult but can also enhance the susceptibility of females to autoimmunity.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
