title: Epigenetic Dysfunction in Turner Syndrome Immune Cells.
abstract: Turner syndrome (TS) is a chromosomal condition associated with partial or complete absence of the X chromosome that involves characteristic findings in multiple organ systems. In addition to well-known clinical characteristics such as short stature and gonadal failure, TS is also associated with T cell immune alterations and chronic otitis media, suggestive of a possible immune deficiency. Recently, ubiquitously transcribed tetratricopeptide repeat on the X chromosome (UTX), a histone H3 lysine 27 (H3K27) demethylase, has been identified as a downregulated gene in TS immune cells. Importantly, UTX is an X-linked gene that escapes X-chromosome inactivation and thus is haploinsufficient in TS. Mice with T cell-specific UTX deficiency have impaired clearance of chronic viral infection due to decreased frequencies of T follicular helper (Tfh) cells, which are critical for B cell antibody generation. In parallel, TS patients have decreased Tfh frequencies in peripheral blood. Together, these findings suggest that haploinsufficiency of the X-linked UTX gene in TS T cells underlies an immune deficit, which may manifest as increased predisposition to chronic otitis media.
authors.affiliation: Department of Pediatrics, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Bradly J
authors.initials: BJ
authors.lastname: Thrasher
authors.affiliation: Department of Microbiology/Immunology, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Lee Kyung
authors.initials: LK
authors.lastname: Hong
authors.affiliation: Department of Microbiology/Immunology, Department of Genetics, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Jason K
authors.initials: JK
authors.lastname: Whitmire
authors.affiliation: Department of Pediatrics and Microbiology/Immunology, University of North Carolina, Chapel Hill, NC, USA. masu@email.unc.edu.
authors.forename: Maureen A
authors.initials: MA
authors.lastname: Su
mesh_terms: D000818:Animals; D041321:Chromosomes, Human, X; D057890:Epigenomics; D056466:Histone Demethylases / Q000378:metabolism; D006801:Humans; D013601:T-Lymphocytes / Q000276:immunology; D014424:Turner Syndrome / Q000235:genetics*
chemical_list: D056466:Histone Demethylases
keywords: Epigenetics; T cell; Turner syndrome; UTX; X chromosome