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  • Review Article
  • Published:

Immune modulation in humans: implications for type 1 diabetes mellitus

Nature Reviews Endocrinology volume 10, pages 229–242 (2014)Cite this article

Subjects

Key Points

  • Reduced immune regulation seems to be a feature of a subgroup of individuals with type 1 diabetes mellitus (T1DM)

  • Several genetic risk factors for T1DM are associated with differential functionality of immune modulation

  • Most immune intervention strategies that have been assessed for their efficacy in intervening in the immunopathogenesis of T1DM suppress, rather than modulate, the autoimmune response against pancreatic islets

  • The newly appreciated heterogeneity in T1DM implies that a personalized approach could be used to treat this disease; treatments that modify the immune system might be ideally suited to this purpose

Abstract

Type 1 diabetes mellitus (T1DM) is the result of autoimmune destruction of pancreatic β cells in genetically predisposed individuals with impaired immune regulation. The insufficiency in the modulation of immune attacks on the β cells might be partly due to genetic causes; indeed, several of the genetic variants that predispose individuals to T1DM have functional features of impaired immune regulation. Whilst defects in immune regulation in patients with T1DM have been identified, many patients seem to have immune regulatory capacities that are indistinguishable from those of healthy individuals. Insight into the regulation of islet autoimmunity might enable us to restore immune imbalances with therapeutic interventions. In this Review, we discuss the current knowledge on immune regulation and dysfunction in humans that is the basis of tissue-specific immune regulation as an alternative to generalized immune suppression.

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Figure 1: Natural history of the immunopathogenesis of T1DM.
Figure 2: Imbalances between immune regulation and autoimmunity.
Figure 3: Immune modulation and therapeutic opportunities.
Figure 4: Patient heterogeneity and personalized medicine.

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Authors and Affiliations

  1. Department of Immunohaematology & Blood Transfusion, Leiden University Medical Center, P. O. Box 9600, Leiden, NL-2300 RC, Netherlands

    Bart O. Roep

  2. Department of Immunobiology, King's College London, School of Medicine, London, SE1 9RT, UK

    Timothy I. M. Tree

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Both authors contributed equally to all aspects of the manuscript.

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Correspondence to Bart O. Roep.

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Competing interests

B. O. Roep has consulted for Andromeda Biotech, Diamyd Medical, GlaxoSmithKline and Lilly. B. O. Roep has performed contract research for Andromeda Biotech and Bayhill Therapeutics. T. I. M. Tree declares no competing interests.

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Roep, B., Tree, T. Immune modulation in humans: implications for type 1 diabetes mellitus. Nat Rev Endocrinol 10, 229–242 (2014). https://doi.org/10.1038/nrendo.2014.2

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