Lab Members

Research Associates:

Tom Van Belle - Research Scientist

Type I diabetes mellitus (T1D) is a chronic autoimmune disorder of the pancreas that precipitates in genetically susceptible individuals by environmental factors. Current symptomatic treatments require daily blood glucose monitoring and injections of insulin. It is critical to develop therapies that can specifically induce long-lasting control over the auto(self)-immune response. The mouse studies we are doing in the lab will lead to crucial insight in diabetes etiology that can hopefully be translated to clinical therapies for T1D patients.

Currently under study is the cytokine interleukin-21 (IL-21) that is produced at higher levels in the pancreas as diabetes develops. We already that two genetically diverse and mechanistically distinct mouse models rendered deficient in the IL-21 receptor are completely diabetes resistant. Therefore, we are currently investigating the mechanisms responsible for this crucial contribution of IL-21 signaling to T1D, and exploring the therapeutic potential of IL-21 blockade in vivo. Given the pleiotropic nature of IL-21, we postulate that the complete absence of diabetes in IL-21R deficient mice is due to several defects, which encompass trafficking, expansion, differentiation, CD4 help and APC function.

One part of our research addresses the biological actions of IL-21 during Type 1 diabetes. As such, the influence of IL-21 on autoaggressive T cells during T1D development is addressed by measuring chemokine levels and the proliferation and pancreatic infiltration of (transferred) autoreactive CD4 and CD8 T cells. Furthermore, we study the role of IL-21 in CD4 helper T cell responses at several levels: does IL-21 play a role in the CD4 help to CD8 T cells, does IL-21 act directly on Tregs or does it render autoreactive T cells resistant to suppression by Tregs?

These fundamental immunologic studies are done in support of preventive and interventional studies of blocking IL-21R in NOD models. We will block IL-21 in combination therapy with islet-antigen specific methods of diabetes prevention and reversion that are currently in clinical trials as monotherapies. Based on current preclinical and clinical data, it is unlikely that any Treg-inducing islet-antigen specific vaccine can revert diabetes alone. Thus, combination with systemically acting immune modulatory agents is a logical extension to enhance efficacy through synergy, as this has been shown in the past by our group.