480 Trim32 deficiency enhances Th2 immunity and predisposes to features of atopic dermatitis

Abstract

Atopic dermatitis is a common cutaneous disorder characterized by severe itch, chronic inflammation and increased nerve fiber density. It has been assumed that the neural changes are in response to ongoing inflammation. We used in vivo imaging of fluorescently labeled peripheral sensory nerves over time during epicutaneous sensitization to ovalbumin in an allergic mouse model of atopic dermatitis. Visualization of the same cutaneous nerve branches and blood vessels sequentially over months revealed that peripheral sensory nerves begin to pathfind within 48 hours of antigen exposure and results in higher innervation density and arbor complexity of neuropeptidergic fibers in the skin within days. Neural sprouting preceded changes in vascularization, vascular permeability, and immune infiltration. Blocking neural activation during periods of sensitization prevented ovalbumin-induced changes in neural recruitment and pattern reorganization as well as subsequent inflammatory infiltrate, scratching behavior. These data implicate different roles for recently identified itch molecules in modulating various steps in the inflammatory response. Thus, in contrast to the traditional view that neural changes are reactive to inflammation and scratching, our data suggest that allergic stimulation in a chronic eczema model actually requires neural recruitment and activation for the elaboration and maintenance of the inflammatory cascade.