On the Role IL-4/IL-13 Heteroreceptor Plays in Regulation of Type 1 Diabetes.
Tobechukwu K UkahAlexis N Cattin-RoyWeirong ChenMindy M MillerSubhasis BarikHabib ZaghouaniPublished in: Journal of immunology (Baltimore, Md. : 1950) (2017)
Type 1 diabetes (T1D) manifests when the insulin-producing pancreatic β cells are destroyed as a consequence of an inflammatory process initiated by lymphocytes of the immune system. The NOD mouse develops T1D spontaneously and serves as an animal model for human T1D. The IL-4Rα/IL-13Rα1 heteroreceptor (HR) serves both IL-4 and IL-13 cytokines, which are believed to function as anti-inflammatory cytokines in T1D. However, whether the HR provides a responsive element to environmental (i.e., physiologic) IL-4/IL-13 in the regulation of peripheral tolerance and the development of T1D has yet to be defined. In this study, NOD mice deficient for the HR have been generated by means of IL-13Rα1 gene disruption and used to determine whether such deficiency affects the development of T1D. Surprisingly, the findings indicate that NOD mice lacking the HR (13R-/-) display resistance to T1D as the rise in blood glucose level and islet inflammation were significantly delayed in these HR-deficient relative to HR-sufficient (13R+/+) mice. In fact, the frequency and spleen-to-pancreas dynamics of both Th1 and Th17 cells were affected in 13R-/- mice. This is likely due to an increase in the frequency of mTGFβ+Foxp3int regulatory T cells and the persistence of CD206+ macrophages in the pancreas as both types of cells confer resistance to T1D upon transfer to 13R+/+ mice. These findings reveal new insights as to the role environmental IL-4/IL-13 and the HR play in peripheral tolerance and the development of T1D.
Keyphrases
- type diabetes
- regulatory t cells
- induced apoptosis
- blood glucose
- oxidative stress
- endothelial cells
- gene expression
- cell death
- cell cycle arrest
- immune response
- risk assessment
- dendritic cells
- glycemic control
- copy number
- metabolic syndrome
- wild type
- signaling pathway
- human health
- pi k akt
- induced pluripotent stem cells