Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza Italy.
European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza Ital.
Expert Rev Clin Immunol. 2022 May;18(5):429-437. doi: 10.1080/1744666X.2022.2060203. Epub 2022 Apr 26.
Autoimmune diseases mostly affect females. Besides hormones, several factors related to chromosome X have been called in action to explain this sex predominance.
This paper provides an overview on the role of chromosome X (chrX) in explaining why females have higher susceptibility to autoimmunity. The work outlines some essential concepts regarding chrX inactivation, escape from chrX inactivation and the evolutionary history of chrX. In addition, we will discuss the concept of gene escape in immune cells, with examples related to specific X-linked genes and autoimmune diseases.
There is growing evidence that many genes present on chrX escape inactivation, and some of them have significant immune-mediated functions. In immune cells of female individuals the escape of these genes is not constant, but the knowledge of the mechanisms controlling this plasticity are not completely understood. Future studies aimed at the characterization of these modifications at single-cell resolution, together with conformational 3D studies of the inactive X chromosome, will hopefully help to fill this gap of knowledge.
自身免疫性疾病主要影响女性。除了激素外，与 X 染色体相关的几个因素也被认为与这种性别优势有关。
本文概述了 X 染色体（chrX）在解释女性为何更容易患自身免疫性疾病方面的作用。该工作概述了一些关于 chrX 失活、chrX 失活逃逸和 chrX 进化历史的基本概念。此外，我们还将讨论免疫细胞中基因逃逸的概念，并举例说明与特定 X 连锁基因和自身免疫性疾病相关的基因逃逸。
越来越多的证据表明，chrX 上存在许多逃避失活的基因，其中一些具有重要的免疫介导功能。在女性个体的免疫细胞中，这些基因的逃逸并非一成不变，但其调控机制尚不完全清楚。未来旨在对这些修饰进行单细胞分辨率特征分析的研究，以及对失活 X 染色体的构象 3D 研究，有望有助于填补这一知识空白。
