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The role of inflammation in insulitis and β-cell loss in type 1 diabetes

Nature Reviews Endocrinology volume 5, pages 219–226 (2009)Cite this article

Abstract

Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease with a strong inflammatory component. The latest studies indicate that innate immunity and inflammatory mediators have a much broader role in T1DM than initially assumed. Inflammation might contribute to early induction and amplification of the immune assault against pancreatic β cells and, at later stages, to the stabilization and maintenance of insulitis. Inflammatory mediators probably contribute to the suppression of β-cell function and subsequent apoptosis; they may also inhibit or stimulate β-cell regeneration and might cause peripheral insulin resistance. The different effects of inflammation take place in different phases of the course of T1DM, and should be considered in the context of a 'dialog' between invading immune cells and the target β cells. This dialog is mediated both by cytokines and chemokines that are released by β cells and immune cells, and by putative, immunogenic signals that are delivered by dying β cells. In this Review, we divided the role of inflammation in T1DM into three arbitrary stages: induction, amplification and maintenance or resolution of insulitis. These stages, and their progression or resolution, might depend on a patient's genetic background, which contributes to disease heterogeneity.

Key Points

  • Innate immunity and inflammatory mediators have a broad and important role in the pathogenesis of type 1 diabetes mellitus

  • Activation of both endogenous and exogenous ligands of pattern-recognition receptors can induce islet inflammation and death of pancreatic β cells

  • Amplification of insulitis might depend on a 'dialog' between immune cells and β cells that is mediated by local production of chemokines and cytokines, and danger signals from dying β cells

  • After transition to adaptive immune response, inflammatory mediators, such as cytokines, might contribute to prolonged functional suppression and death of β cells, modulation of β-cell regeneration and insulin resistance

  • Some inflammatory mediators might promote the survival and proliferation of β cells, especially in the absence of autoimmune reaction

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Figure 1: Inflammatory processes that might contribute to T1DM.
Figure 2: Interaction of β cells and immune cells leads to induction and amplification of insulitis, and the transition from innate to adaptative immune response.

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Acknowledgements

This Review is partially based on a lecture given by DL Eizirik at the 13th European Association for the Study of Diabetes/Juvenile Diabetes Research Foundation Oxford Workshop, Oxford, UK, 8–11 August 2008. The concepts presented in this article were developed by the authors during research supported by the European Union (STREP SaveBeta, contract no. 036,903; Framework Program 6 of the European Community), the Fonds National de la Recherche Scientifique, Actions de Recherche Concerté de la Communauté Française, Belgium and the Belgium Program on Interuniversity Poles of Attraction initiated by the Belgian State (IUAP P5/17 and P6/40). M Colli is the recipient of a scholarship from the Brazilian Coordination for the Improvement of Higher Education Personnel.

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  1. Laboratory of Experimental Medicine, Medical Faculty, Université Libre de Bruxelles (ULB), Brussels, Belgium

    Décio L. Eizirik, Maikel L. Colli & Fernanda Ortis

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Eizirik, D., Colli, M. & Ortis, F. The role of inflammation in insulitis and β-cell loss in type 1 diabetes. Nat Rev Endocrinol 5, 219–226 (2009). https://doi.org/10.1038/nrendo.2009.21

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