On the aetiopathogenesis of type 1 diabetes: key roles for innate immunity and dietary antigens?

Summary

A key characteristic of human “auto”immune disease is the focus on a few target autoantigens. This phylogenetically conserved antigenic restriction is consistent with the concept that the non adaptive innate immune system is critical to disease development. Indeed, defects of macrophages, dendritic cells or NK T cells have been reported for type 1 diabetes or its animal models. Products of the innate immune system, such as IL-12, IL-15 and IL-18 have been shown to drive destructive insulitis. Besides the modulatory impact of infections a key environmental factor appears to be the diet. Wheat, soy and cow milk may contain diabetogenic proteins, as judged from animal experiments. These findings indicate a key role of the gut immune system which probably exhibits deficient oral tolerance mechanisms and therefore would mount a proinflammatory response when challenged with putative diabetogenic compounds in the diet. Dietary intervention studies to modulate the natural course of type 1 diabetes are underway.

Key words

Aetiology of type 1 diabetes - innate immunity - diet - autoimmunity