# The X Factor in Immunity: Sex Differences Shaped by the X Chromosome

## TL;DR

This paper explores how sex differences in immunity are influenced by the X chromosome and sex hormones, aiming to improve sex-specific treatments for immune-related diseases.

## Contribution

The paper highlights recent insights into X-linked gene regulation and sex hormone effects on immune responses, offering new perspectives for sex-specific therapies.

## Key findings

- Females show stronger immune responses than males due to sex hormones and X chromosome differences.
- X-Chromosome Inactivation (XCI) and selective gene reactivation on the Xi influence immune cell function in females.
- Dosage-sensitive X-linked genes contribute to female-biased autoimmune diseases and immune signaling differences.

## Abstract

There are sex differences with immune responses where females exhibit stronger immune responses compared to males. Both sex hormones and sex chromosome differences between males and females contribute to the observed sex differences with innate and adaptive immune cell composition and function. Here, we present recent findings investigating sex differences with immune cells and responses, highlighting contributions from sex hormones or X‐linked genes. We also review the epigenetic gene regulatory mechanisms that form the inactive X chromosome (Xi), known as X‐Chromosome Inactivation (XCI), the heterochromatic nature of the Xi that allows for selective gene reactivation, and recent work investigating the mechanisms of XCI maintenance in female immune cells. We also highlight some dosage‐sensitive X‐linked genes involved in female‐biased autoimmune disease, discuss sex differences with immune signaling pathways, and sex differences with viral infections and vaccine responses with the ultimate goal to leverage these insights for the development of sex‐specific therapeutic interventions for immune‐related diseases.