The X chromosome in immune functions: when a chromosome makes the difference

Abstract

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.

The brain parenchyma has a type I interferon response that can limit virus spread

“…Mouse Injections. All experiments were performed using 8-9-wk-old male animals to control for age-and sex-dependent variations (71,72). Animals were injected using a stereotaxic instrument (Narishige International USA) and pulled capillary microdispensers (Drummond Scientific) using the following coordinates for the CP: A/P, 1 from bregma, L/M, 1.8; D/V, −2.5.…”

Sex Differences in Health and Survival

“…In addition, the cellular mosaicism in women contributes to physiological diversity, which can be advantageous when encountering new immune challenges (Spolarics 2007;Morris and Harrison 2009). However, X chromosome abnormalities-e.g., extreme inactivation skewing and inactive chromosome reactivation-may also be disadvantageous for females, and may underlie the female preponderance in autoimmunity (Libert et al 2010).…”

Hvorfor er autoimmune sykdommer hyppigere hos kvinner?

“…In recent years it has become clear that the X chromosome plays an important part in the development of autoimmunity (5). The purpose of this paper is to discuss the significance of factors related to the X chromosome for the gender difference in the prevalence of autoimmune diseases.…”

“…Skewed X chromosome inactivation may lead to women mainly having cells that only express X-linked genes from one X chromosome. One explanation for the relationship between skewed X chromosome inactivation and autoimmune disease may be that X-linked autoantigens on the one X chromosome are not sufficiently presented in the thymus or other tissues involved in the induction of tolerancewhereas the expression in peripheral tissues is large enough to trigger the development of autoantibodies (3,5).…”

“…A woman with a defective gene on one X chromosome will most often be unaffected as long as she has a normal copy of the gene on the other X chromosome. The presence of two X chromosomes may be one of the reasons that women generally live longer than men (5,6). However, the price of having two X chromosomes is a higher risk of autoimmune disease.…”