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When the balance is broken: X‐linked gene dosage from two X chromosomes and female‐biased autoimmunity
Author(s) -
Syrett Camille M.,
Anguera Montserrat C.
Publication year - 2019
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.6ri0319-094r
Subject(s) - autoimmunity , biology , x chromosome , immunology , x inactivation , gene , immune system , acquired immune system , immunity , innate immune system , genetics , autoimmune disease , lymphocyte , antibody
Women and men exhibit differences in innate and adaptive immunity, and women are more susceptible to numerous autoimmune disorders. Two or more X chromosomes increases the risk for some autoimmune diseases, and increased expression of some X‐linked immune genes is frequently observed in female lymphocytes from autoimmune patients. Evidence from mouse models of autoimmunity also supports the idea that increased expression of X‐linked genes is a feature of female‐biased autoimmunity. Recent studies have begun to elucidate the correlation between abnormal X‐chromosome inactivation (XCI), an essential mechanism female somatic cells use to equalize X‐linked gene dosage between the sexes, and autoimmunity in lymphocytes. In this review, we highlight research describing overexpression of X‐linked immunity‐related genes and female‐biased autoimmunity in both humans and mouse models, and make connections with our recent work elucidating lymphocyte‐specific mechanisms of XCI maintenance that become altered in lupus patients.