Targeting of IL-2 receptor with a caspase fusion protein disrupts autoimmunity in prediabetic and diabetic NOD mice.

Diabetologia
Shai YarkoniNadir Askenasy

Abstract

Interruption of IL-2 signalling is an attractive therapeutic target in autoimmune disorders. In this study we evaluated the effect of a fusion protein composed of IL-2 and caspase-3 (IL2-cas) on NOD mice, as compared with disease induction by cyclophosphamide. IL2-cas was assessed in NOD mice at various ages and in conjunction with cyclophosphamide administration. The effect of IL2-cas on diabetogenic cells was evaluated in adoptive transfer experiments and in cell suspension in vitro. IL2-cas induced apoptosis in T cells expressing the alpha chain of the IL-2 receptor (cluster of differentiation [CD]25) in vitro, with superior survival of T cells expressing CD4 and forkhead box P3 (FOXP3). The fusion protein decreased mixed lymphocyte reactivity, and pretreatment with IL2-cas decreased the efficacy of adoptive transfer of diabetes into NOD severe combined immunodeficiency mice. Administration of one dose of IL2-cas decreased the incidence of diabetes in NOD mice, showing a superior beneficial effect when administered at young age, and effectively blocked induction of hyperglycaemia by cyclophosphamide, reducing the severity of islet inflammation. Administration of IL2-cas caused an acute increase in CD25(-)FOXP3(+) T cells in ...Continue Reading

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Citations

Jul 9, 2014·Veterinary Immunology and Immunopathology·Tomasz MaślankaJerzy Jan Jaroszewski
Apr 19, 2011·Journal of Autoimmunity·Ayelet KaminitzNadir Askenasy
Jul 14, 2010·Autoimmunity Reviews·Enosh M AskenasyJean-Jaques Askenasy
May 24, 2015·Autoimmunity Reviews·Kostas KakleasKyriaki Karavanaki
Jan 10, 2012·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Shai YarkoniNadir Askenasy

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