β Cell Hypoxia-Inducible Factor-1α Is Required for the Prevention of Type 1 Diabetes
Publication date: 21 May 2019Source: Cell Reports, Volume 27, Issue 8Author(s): Amit Lalwani, Joanna Warren, David Liuwantara, Wayne J. Hawthorne, Philip J. O’Connell, Frank J. Gonzalez, Rebecca A. Stokes, Jennifer Chen, D. Ross Laybutt, Maria E. Craig, Michael M. Swarbrick, Cecile King, Jenny E. GuntonSummaryThe development of autoimmune disease type 1 diabetes (T1D) is determined by both genetic background and environmental factors. Environmental triggers include RNA viruses, particularly coxsackievirus (CV), but how they induce T1D is not understood. Here, we demonstrate that deletion of the transcription factor hypoxia-inducible factor-1α (HIF-1α) from β cells increases the susceptibility of non-obese diabetic (NOD) mice to environmentally triggered T1D from coxsackieviruses and the β cell toxin streptozotocin. Similarly, knockdown of HIF-1α in human islets leads to a poorer response to coxsackievirus infection. Studies in coxsackievirus-infected islets demonstrate that lack of HIF-1α leads to impaired viral clearance, increased viral load, inflammation, pancreatitis, and loss of β cell mass. These findings show an important role for β cells and, specifically, lack of β cell HIF-1α in the development of T1D. These data suggest new strategies for the prevention of T1D.Graphical Abstract
Source: Cell Reports - Category: Cytology Source Type: research
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