Nerve-Langerhans cell interactions in diabetes and aging.

Cutaneous infections are a leading cause of hospitalization of diabetic patients. Langerhans cells (LCs) are antigen-presenting cutaneous dendritic cells that protect against infections, and effects of diabetes and aging on these cells are unclear. We examined LCs in footpads of rats with streptozotocin-induced diabetes at 3 months of age following 4 weeks of diabetes, and at 6 months following 16 weeks of diabetes. Immunostaining of LCs using the selective marker protein langerin showed cutaneous LC composition increased between 3 and 6 months of age owing to increased LC numbers and size in control rats. In diabetic rats, LC numbers increased with age but, unlike 6 month old controls, cell size did not, suggesting that diabetes impairs the increase in cell size that is a hallmark of LC maturation. Diabetes reduced LC numbers after 4 weeks and numbers and sizes following 16 weeks. We examined the relation between LC and innervation and found that, while axon density decreased with aging, it was not affected by 16 weeks of diabetes. However, LCs expressing the neuronal marker PGP9.5 represented a source of error in axonal counts. These findings support the hypothesis that diabetes substantially impacts LC proliferation and maturation independent of effects on cutaneous innervation. Accordingly, the interactions of diabetes and aging on LCs may be important factors in predisposing diabetic patients to cutaneous ulcers and infections.