Dataset Information

An ancestral retroviral protein identified as a therapeutic target in type-1 diabetes.

ABSTRACT: Human endogenous retroviruses (HERVs), remnants of ancestral viral genomic insertions, are known to represent 8% of the human genome and are associated with several pathologies. In particular, the envelope protein of HERV-W family (HERV-W-Env) has been involved in multiple sclerosis pathogenesis. Investigations to detect HERV-W-Env in a few other autoimmune diseases were negative, except in type-1 diabetes (T1D). In patients suffering from T1D, HERV-W-Env protein was detected in 70% of sera, and its corresponding RNA was detected in 57% of peripheral blood mononuclear cells. While studies on human Langerhans islets evidenced the inhibition of insulin secretion by HERV-W-Env, this endogenous protein was found to be expressed by acinar cells in 75% of human T1D pancreata. An extensive immunohistological analysis further revealed a significant correlation between HERV-W-Env expression and macrophage infiltrates in the exocrine part of human pancreata. Such findings were corroborated by in vivo studies on transgenic mice expressing HERV-W-env gene, which displayed hyperglycemia and decreased levels of insulin, along with immune cell infiltrates in their pancreas. Altogether, these results strongly suggest an involvement of HERV-W-Env in T1D pathogenesis. They also provide potentially novel therapeutic perspectives, since unveiling a pathogenic target in T1D.

SUBMITTER: Levet S

PROVIDER: S-EPMC5621895 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

An ancestral retroviral protein identified as a therapeutic target in type-1 diabetes.

Levet Sandrine S Medina Julie J Joanou Julie J Demolder Amandine A Queruel Nelly N Réant Kevin K Normand Matthieu M Seffals Marine M Dimier Julie J Germi Raphaële R Piofczyk Thomas T Portoukalian Jacques J Touraine Jean-Louis JL Perron Hervé H

JCI insight 20170907 17

Human endogenous retroviruses (HERVs), remnants of ancestral viral genomic insertions, are known to represent 8% of the human genome and are associated with several pathologies. In particular, the envelope protein of HERV-W family (HERV-W-Env) has been involved in multiple sclerosis pathogenesis. Investigations to detect HERV-W-Env in a few other autoimmune diseases were negative, except in type-1 diabetes (T1D). In patients suffering from T1D, HERV-W-Env protein was detected in 70% of sera, and ...[more]

PMID: 28878130

Similar Datasets

Project description:Objective: Non-alcoholic fatty liver disease (NAFLD) is a serious health threat worldwide. The aim of this study was to comprehensively describe the metabolic and immunologic characteristics of NAFLD, and to explore potential therapeutic drug targets for NAFLD. Methods: Six NAFLD datasets were downloaded from the Gene Expression Omnibus (GEO) database, including GSE48452, GSE63067, GSE66676, GSE89632, GSE24807, and GSE37031. The datasets we then used to identify and analyze genes that were differentially expressed in samples from patients with NAFLD and normal subjects, followed by analysis of the metabolic and immunologic characteristics of patients with NAFLD. We also identified potential therapeutic drugs for NAFLD using the Connectivity Map (CMAP) database. Moreover, we constructed a prediction model using minimum depth random forest analysis and screened for potential therapeutic targets. Finally, therapeutic targets were verified in a fatty liver model stimulated by palmitic acid (PA). Results: A total of 1,358 differentially expressed genes (DEGs) were obtained, which were mainly enriched in carbohydrate metabolism, lipid metabolism, and other metabolic pathways. Immune infiltration analysis showed that memory B cells, regulatory T cells and M1 macrophage were significantly up-regulated, while T cells follicular helper were down regulated in NAFLD. These may provide a reference for the immune-metabolism interaction in the pathogenesis of NAFLD. Digoxin and helveticoside were identified as potential therapeutic drugs for NAFLD via the CMAP database. In addition, a five-gene prediction model based on minimum depth random forest analysis was constructed, and the receiver operating characteristic (ROC) curves of both training and validation set reached 1. The five candidate therapeutic targets were ENO3, CXCL10, INHBE, LRRC31, and OPTN. Moreover, the efficiency of hepatocyte adipogenesis decreased after OPTN knockout, confirming the potential use of OPTN as a new therapeutic target for NAFLD. Conclusion: This study provides a deeper insight into the molecular pathogenesis of NAFLD. We used five key genes to construct a diagnostic model with a strong predictive effect. Therefore, these five key genes may play an important role in the diagnosis and treatment of NAFLD, particularly those with increased OPTN expression.

Dataset Information

An ancestral retroviral protein identified as a therapeutic target in type-1 diabetes.

Publications

An ancestral retroviral protein identified as a therapeutic target in type-1 diabetes.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets