A gene network regulated by the transcription factor VGLL3 as a promoter of sex-biased autoimmune diseases

作者：Liang Yun; Tsoi Lam C; Xing Xianying; Beamer Maria A; Swindell William R; Sarkar Mrinal K; Berthier Celine C; Stuart Philip E; Harms Paul W; Nair Rajan P; Elder James T; Voorhees John J; Kahlenberg J Michelle; Gudjonsson Johann E

来源：Nature Immunology, 2017, 18(2): 152-160.

DOI：10.1038/ni.3643

Autoimmune diseases affect 7.5% of the US population, and they are among the leading causes of death and disability. A notable feature of many autoimmune diseases is their greater prevalence in females than in males, but the underlying mechanisms of this have remained unclear. Through the use of high-resolution global transcriptome analyses, we demonstrated a female-biased molecular signature associated with susceptibility to autoimmune disease and linked this to extensive sex-dependent co-expression networks. This signature was independent of biological age and sex-hormone regulation and was regulated by the transcription factor VGLL3, which also had a strong female-biased expression. On a genome-wide level, VGLL3-regulated genes had a strong association with multiple autoimmune diseases, including lupus, scleroderma and Sjogren's syndrome, and had a prominent transcriptomic overlap with inflammatory processes in cutaneous lupus. These results identified a VGLL3-regulated network as a previously unknown inflammatory pathway that promotes female-biased autoimmunity. They demonstrate the importance of studying immunological processes in females and males separately and suggest new avenues for therapeutic development.

• 出版日期2017-2