UVB exposure triggers autoimmune cutaneous inflammation in Foxp3dExon2-expressing mice.
Ultraviolet B (UVB) light is a common environmental trigger that can induce flares in several autoimmune diseases. Here, we modeled photosensitivity in mice which express an autoimmune-driving isoform of Foxp3 without the second coding exon of the gene, called FoxP3?E2 mice. In the steady-state, FoxP3?E2mice generate keratinocyte-specific IgE autoantibodies and more autoreactive T follicular helper (TFH) cells that target keratinocyte-derived autoantigens that are released upon exposure to damaging doses of UVB. After UVB light challenge in vivo, FoxP3?E2mice generated more IgE antibodies, increased germinal center formation, had higher percentages of IL-4+TFHs, developed worsened skin pathology and had higher concentrations of IgE in UVB-damaged skin. We also observed a significant increase in IgE on basophils and accumulation of basophil extracellular traps in UVB-challenged skin of FoxP3?E2mice. Collectively, FoxP3?E2mice fail to maintain self-tolerance in GCs, causing IgE autoantibody production and driving exaggerated photosensitivity. Overall design: Foxp3-WT and Foxp3-DE2 mice were treated with 6 doses of UVB light (100mJ/cm2) on a shaved patch of skin (3cm x 2cm) on the back flank of each mouse. Total RNA was extracted from skin from the UVB-treated site (+UVB) and a non-treated control site (-UVB) and processed for bulk RNA sequencing.