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Article Dans Une Revue Diabetes Année : 2013

Limitations of IL-2 and Rapamycin in Immunotherapy of Type 1 Diabetes

Résumé

Administration of low-dose interleukin-2 (IL-2) alone or combined with rapamycin (RAPA) prevents hyperglycemia in NOD mice. Also, low-dose IL-2 cures recent-onset type 1 diabetes (T1D) in NOD mice, partially by boosting pancreatic regulatory T cells (Treg cells). These approaches are currently being evaluated in humans. Our objective was to study the effect of higher IL-2 doses (250,000-500,000 IU daily) as well as low-dose IL-2 (25,000 IU daily) and RAPA (1 mg/kg daily) (RAPA/IL-2) combination. We show that, despite further boosting of Treg cells, high doses of IL-2 rapidly precipitated T1D in prediabetic female and male mice and increased myeloid cells in the pancreas. Also, we observed that RAPA counteracted IL-2 effects on Treg cells, failed to control IL-2-boosted NK cells, and broke IL-2-induced tolerance in a reversible way. Notably, the RAPA/IL-2 combination failure to cure T1D was associated with an unexpected deleterious effect on glucose homeostasis at multiple levels, including β-cell division, glucose tolerance, and liver glucose metabolism. Our data help to understand the therapeutic limitations of IL-2 alone or RAPA/IL-2 combination and could lead to the design of improved therapies for T1D.

Dates et versions

hal-02565238 , version 1 (06-05-2020)

Identifiants

Citer

Audrey Baeyens, Louis Pérol, Gwladys Fourcade, Nicolas Cagnard, Wassila Carpentier, et al.. Limitations of IL-2 and Rapamycin in Immunotherapy of Type 1 Diabetes. Diabetes, 2013, 62 (9), pp.3120-3131. ⟨10.2337/db13-0214⟩. ⟨hal-02565238⟩
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