1. HERV1-env Induces Unfolded Protein Response Activation in Autoimmune Liver Disease: A Potential Mechanism for Regulatory T Cell Dysfunction
- Author
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Kumar Subramanian, Saikat Paul, Andrew Libby, Jordan Patterson, Adam Arterbery, James Knight, Christopher Castaldi, Guilin Wang, Yaron Avitzur, Mercedes Martinez, Steve Lobritto, Yanhong Deng, Gan Geliang, Alexander Kroemer, Thomas Fishbein, Andrew Mason, Margarita Dominguez-Villar, Malaiyalam Mariappan, and Udeme D. Ekong
- Subjects
Immunology ,Immunology and Allergy - Abstract
Regulatory T cells (Tregs) are not terminally differentiated but can acquire effector properties. Here we report an increased expression of human endogenous retrovirus 1 (HERV1-env) proteins in Tregs of patients with de novo autoimmune hepatitis and autoimmune hepatitis, which induces endoplasmic reticulum (ER) stress. HERV1-env-triggered ER stress activates all three branches (IRE1, ATF6, and PERK) of the unfolded protein response (UPR). Our coimmunoprecipitation studies show an interaction between HERV1-env proteins and the ATF6 branch of the UPR. The activated form of ATF6α activates the expression of RORC and STAT3 by binding to promoter sequences and induces IL-17A production. Silencing of HERV1-env results in recovery of Treg suppressive function. These findings identify ER stress and UPR activation as key factors driving Treg plasticity (species: human).
- Published
- 2023
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