Viral infections in type 1 diabetes mellitus—why the β cells?

A Op de Beeck, DL Eizirik - Nature Reviews Endocrinology, 2016 - nature.com
A Op de Beeck, DL Eizirik
Nature Reviews Endocrinology, 2016nature.com
Type 1 diabetes mellitus (T1DM) is caused by progressive autoimmune-mediated loss of
pancreatic β-cell mass via apoptosis. The onset of T1DM depends on environmental factors
that interact with predisposing genes to induce an autoimmune assault against β cells.
Epidemiological, clinical and pathology studies in humans support viral infection—
particularly by enteroviruses (for example, coxsackievirus)—as an environmental trigger for
the development of T1DM. Many candidate genes for T1DM, such as MDA5, PTPN2 and …
Abstract
Type 1 diabetes mellitus (T1DM) is caused by progressive autoimmune-mediated loss of pancreatic β-cell mass via apoptosis. The onset of T1DM depends on environmental factors that interact with predisposing genes to induce an autoimmune assault against β cells. Epidemiological, clinical and pathology studies in humans support viral infection—particularly by enteroviruses (for example, coxsackievirus)—as an environmental trigger for the development of T1DM. Many candidate genes for T1DM, such as MDA5, PTPN2 and TYK2, regulate antiviral responses in both β cells and the immune system. Cellular permissiveness to viral infection is modulated by innate antiviral responses that vary among different tissues or cell types. Some data indicate that pancreatic islet α cells trigger a more efficient antiviral response to infection with diabetogenic viruses than do β cells, and so are able to eradicate viral infections without undergoing apoptosis. This difference could account for the varying ability of islet-cell subtypes to clear viral infections and explain why chronically infected pancreatic β cells, but not α cells, are targeted by an autoimmune response and killed during the development of T1DM. These issues and attempts to target viral infection as a preventive therapy for T1DM are discussed in the present Review.
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