TY - JOUR AU - Levet, Sandrine AU - Medina, Julie AU - Joanou, Julie AU - Demolder, Amandine AU - Queruel, Nelly AU - Réant, Kevin AU - Normand, Matthieu AU - Seffals, Marine AU - Dimier, Julie AU - Germi, Raphaële AU - Piofczyk, Thomas AU - Portoukalian, Jacques AU - Touraine, Jean-Louis AU - Perron, Hervé T1 - An ancestral retroviral protein identified as a therapeutic target in type-1 diabetes PY - 2017/09/07/ AB - 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. JF - JCI Insight JA - JCI Insight SN - 2379-3708 DO - 10.1172/jci.insight.94387 VL - 2 IS - 17 UR - https://doi.org/10.1172/jci.insight.94387 PB - The American Society for Clinical Investigation ER -