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Current Diabetes Reports

, 14:553 | Cite as

Interleukin 2 in the Pathogenesis and Therapy of Type 1 Diabetes

  • Michelle Rosenzwajg
  • Guillaume Churlaud
  • Agnès Hartemann
  • David Klatzmann
Pathogenesis of Type 1 Diabetes (A Pugliese, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Pathogenesis of Type 1 Diabetes

Abstract

Regulatory T cells (Tregs) play a major role in controlling effector T cells (Teffs) responding to self-antigens, which cause autoimmune diseases. An improper Treg/Teff balance contributes to most autoimmune diseases, including type 1 diabetes (T1D). To restore a proper balance, blocking Teffs with immunosuppressants has been the only option, which was partly effective and too toxic. It now appears that expanding/activating Tregs with low-dose interleukin-2 (IL-2) could provide immunoregulation without immunosuppression. This is particularly interesting in T1D as Tregs from T1D patients are reported as dysfunctional and a relative deficiency in IL-2 production and/or IL-2-mediated signaling could contribute to this phenotype. A clinical study of low-dose IL-2 showed a very good safety profile and good Treg expansion/activation in T1D patients. This opens the way for efficacy trials to test low-dose IL-2 in prevention and treatment of T1D and to establish in which condition restoration of a proper Treg/Teff balance would be beneficial in the field of autoimmune and inflammatory diseases.

Keywords

Tolerance Immunotherapy Autoimmune disease Inflammation Pharmacokinetics 

Notes

Acknowledgments

This work was supported by our academic institution (AP-HP, UPMC, INSERM), by the Inflammation-Immunopathology-Biotherapy Department (DHU i2B; http://www.dhu-i2b.fr), by French state funds managed by the ANR within the “Investissements d’Avenir” program under reference ANR-11-IDEX-0004-02, and by DIABIL-2, part of the Seventh Framework Program collaborative project for type 1 diabetes under the grant agreement #305380 (http://www.diabil-2.eu).

Compliance with Ethics Guidelines

Conflict of Interest

Michelle Rosenzwajg is a shareholder of ILTOO Pharma and is an inventor on a patent application related to the therapeutic use of low-dose IL-2, which belongs to her academic institution and has been licensed to ILTOO Pharma. Guillaume Churlaud is a shareholder of ILTOO Pharma. Agnès Hartemann declares that she has no conflict of interest. David Klatzmann is a shareholder of ILTOO Pharma and is an inventor on a patent application related to the therapeutic use of low-dose IL-2, which belongs to his academic institution and has been licensed to ILTOO Pharma.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Michelle Rosenzwajg
    • 1
    • 2
    • 3
  • Guillaume Churlaud
    • 1
    • 2
    • 3
  • Agnès Hartemann
    • 4
  • David Klatzmann
    • 1
    • 2
    • 3
  1. 1.Biotherapy (CIC-BTi) and Inflammation-Immunopathology-Biotherapy Department (i2B), AP-HPHôpital Pitié-SalpêtrièreParisFrance
  2. 2.Department of Immunology-Immunopathology-Immunotherapy (I3)Sorbonne Universités, UPMC Univ Paris 06, UMRS 959ParisFrance
  3. 3.Department of Immunology-Immunopathology-Immunotherapy (I3)INSERM, UMRS 959ParisFrance
  4. 4.Department of Diabetology, AP-HPHôpital Pitié-SalpêtrièreParisFrance

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