Grant: Travel Awards - Institute Community Support

Ultraviolet B (UVB) light is an environmental trigger of flares in several autoimmune diseases. Here, we modeled photosensitivity in FoxP3[delta]E2 mice, which express an autoimmune-driving isoform of Foxp3 without the second coding exon of the gene. The FoxP3[delta]E2 is expressed in higher frequencies in several different autoimmune diseases, but how this isoform of Foxp3 impacts immune responses to environmental stimuli is not understood. In the steady-state, FoxP3[delta]E2 mice generate skin-specific autoantibodies. After the skin is challenged with damaging doses of UVB light, FoxP3[delta]E2 mice had increased immune activity in draining lymph nodes, increased production of autoantibodies, worsened skin pathology and higher concentrations of autoantibodies in UVB-treated skin. Furthermore, depletion of specific subclasses of autoantibodies attenuated some of the phenotypes associated with increased skin inflammation. Collectively, FoxP3[delta]E2 mice fail to maintain self-tolerance to skin antigens, causing autoantibody production and susceptibility to autoimmune-like photosensitivity.