Islet inflammation (insulitis) in type 1 diabetes mellitus is triggered by a deleterious dialogue between β-cells and the immune system, inducing β-cell dysfunction and death. This concept, outlined in our 2009 Review, has been confirmed and extended. Here, we provide a brief update of the field and outline key pending questions.
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References
Eizirik, D. L., Colli, M. L. & Ortis, F. The role of inflammation in insulitis and β-cell loss in type 1 diabetes. Nat. Rev. Endocrinol. 5, 219–226 (2009).
Oram, R. A., Sims, E. K. & Evans-Molina, C. Beta cells in type 1 diabetes: mass and function; sleeping or dead? Diabetologia 62, 567–577 (2019).
Eizirik, D. L., Pasquali, L. & Cnop, M. Pancreatic β-cells in type 1 and type 2 diabetes mellitus: different pathways to failure. Nat. Rev. Endocrinol. 16, 349–362 (2020).
Ramos-Rodríguez, M. et al. The impact of proinflammatory cytokines on the β-cell regulatory landscape provides insights into the genetics of type 1 diabetes. Nat. Genet. 51, 1588–1595 (2019).
James, E. A., Mallone, R., Kent, S. C. & DiLorenzo, T. P. T-cell epitopes and neo-epitopes in type 1 diabetes: a comprehensive update and reappraisal. Diabetes 69, 1311–1335 (2020).
Op de Beeck, A. & Eizirik, D. L. Viral infections in type 1 diabetes mellitus — why the β cells? Nat. Rev. Endocrinol. 12, 263–273 (2016).
Marroqui, L. et al. Interferon-α mediates human beta cell HLA class I overexpression, endoplasmic reticulum stress and apoptosis, three hallmarks of early human type 1 diabetes. Diabetologia 60, 656–667 (2017).
Coomans de Brachène, A. et al. Preclinical evaluation of tyrosine kinase 2 inhibitors for human beta-cell protection in type 1 diabetes. Diabetes Obes. Metab. https://doi.org/10.1111/dom.14104 (2020).
Colli, M. L. et al. An integrated multi-omics approach identifies the landscape of interferon-α-mediated responses of human pancreatic beta cells. Nat. Commun. 11, 2584 (2020).
Hostens, K. et al. Exposure of human islets to cytokines can result in disproportionately elevated proinsulin release. J. Clin. Invest. 104, 67–72 (1999).
Acknowledgements
The authors acknowledge the support of grants from the JDRF (2-SRA-2019-834-S-B); Welbio and Fonds National de la Recherche Scientifique (FNRS), Belgium, grants CR-2015A-06 and CR-2019C-04; Innovate2CureType1-Dutch Diabetes Research Fundation (DDRF); and start-up funding provided by the Indiana Biosciences Research Institute. D.L.E. has also received funding from the Innovative Medicines Initiative Joint Undertaking under grant agreements nos 115797 and 945268 (INNODIA and INNODIA HARVEST). This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and “EFPIA”, “JDRF” and “The Leona M. and Harry B. Helmsley Charitable Trust”.
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Eizirik, D.L., Colli, M.L. Revisiting the role of inflammation in the loss of pancreatic β-cells in T1DM. Nat Rev Endocrinol 16, 611–612 (2020). https://doi.org/10.1038/s41574-020-00409-6
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DOI: https://doi.org/10.1038/s41574-020-00409-6
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