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.
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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).
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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.
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This article is part of the Topical Collection on Pathogenesis of Type 1 Diabetes
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Rosenzwajg, M., Churlaud, G., Hartemann, A. et al. Interleukin 2 in the Pathogenesis and Therapy of Type 1 Diabetes. Curr Diab Rep 14, 553 (2014). https://doi.org/10.1007/s11892-014-0553-6
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DOI: https://doi.org/10.1007/s11892-014-0553-6