Transposable element dysregulation in systemic lupus erythematosus and regulation by histone conformation and Hsp90

Clinical Immunology : the Official Journal of the Clinical Immunology Society
Maurer KellyE Sullivan Kathleen

Abstract

Systemic lupus erythematosus (SLE) represents an autoimmune disease in which activation of the type I interferon pathway leads to dysregulation of tolerance and the generation of autoantibodies directed against nuclear constituents. The mechanisms driving the activation of the interferon pathway in SLE have been the subject of intense investigation but are still incompletely understood. Transposable elements represent an enormous source of RNA that could potentially stimulate the cell intrinsic RNA-recognition pathway, leading to upregulation of interferons. We used RNA-seq to define transposable element families and subfamilies in three cell types in SLE and found diverse effects on transposable element expression in the three cell types and even within a given family of transposable elements. When potential mechanisms were examined, we found that Hsp90 inhibition could drive increased expression of multiple type of transposable elements. Both direct inhibition and the delivery of a heat shock itself, which redirects heat shock regulators (including Hsp90) off of basal expression promoters and onto heat shock-responsive promoters, led to increased transposable element expression. This effect was amplified by the concurrent del...Continue Reading

Citations

Jun 18, 2019·Lupus Science & Medicine·Mary K Crow, Lars Ronnblom
Jun 4, 2020·International Journal of Molecular Sciences·Amit SharmaMartina C Herwig-Carl
Mar 7, 2021·Journal of Clinical Medicine·Kennedy C Ukadike, Tomas Mustelin
Apr 24, 2021·RNA·Ana Gazquez-GutierrezSara Macias

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Autoimmune diseases occur as a result of an attack by the immune system on the body’s own tissues resulting in damage and dysfunction. There are different types of autoimmune diseases, in which there is a complex and unknown interaction between genetics and the environment. Discover the latest research on autoimmune diseases here.

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