The role of IL-7 and IL-7/IL-2 receptor isoforms in the development of autoimmune T cells in children with type 1 diabetes

Type 1 diabetes (T1D) is an autoimmune disease in which the immune system destroys the pancreatic beta islet cells leading to a life-long dependance on insulin therapy.

Autoantigen specific effector CD4+ T cells (Teff) of a TH1 phenotype support the development of autoimmune diseases and play a key role in the pathogenesis of type-1 diabetes. Regulatory T cells (Treg) can prevent development and progress of autoimmune diseases. Previous studies elucidated the interplay between these T-cell subsets, especially in the context of two key cytokines IL-7 and IL-2 and their receptors.

IL-7 has various effects on T cells including induction of effector T cells of a TH1 phenotype and suppressing the development of regulatory T cells. However, the mechanisms how IL-7 influences the generation of regulatory T cells are hardly defined. IL-2 primarily supports the development of regulatory T cells, which in principle can prevent the development of type 1 diabetes (T1D). T-cell regulation of IL-7 and IL-2 pathways takes place at several levels including membrane receptor expression, release of soluble receptor chains, IL-2 cytokine expression, and modulation of cytokine receptor signaling.

The aim of our study is to characterize the effects of IL-7 during in vitro T-cell activation on membrane-bound and soluble cytokine receptor expression, cytokine production, and regulators of cytokine signaling. This approach may lead to the identification of candidate targets for dysregulated T-cell functions leading to T1D.

Researchers: Julia Seyfarth, Katharina Förtsch, Heinz Ahlert