Foxp3 exon 2 regulates keratinocyte-specific IgE and basophil extracellular traps in cutaneous autoimmune photosensitivity.

Abstract Ultraviolet B (UVB) light is a common environmental trigger that can induce flares in several autoimmune diseases, but the mechanisms mediate UVB-induced photosensitivity remain poorly understood. We used mice which express an autoimmune-driving isoform of Foxp3, called FoxP3 ΔE2mice, to develop model cutaneous photosensitivity. In steady-state, ΔE2mice have high serum titers IgE target skin-associated autoantigens, and increased numbers IL4-producing T follicular helper cells proteins (Keratin 14) absence overt immune challenge. After skin exposure UVB light, had further elevated IgE, worsened inflammation, complex deposition localized challenge site. production UVB-challenged correlated with frequencies germinal center (GC) cells, percentages IL-4 +T basophils surface expression draining lymph nodes skin. also observed significant increase accumulation, Tug8 +basophil extracellular traps activated plasmacytoid dendritic (CD80 +CD86 +) skin-draining when compared wild-type littermates. Collectively, we found regulatory fail maintain self-tolerance GC, resulting reactive inflammation driven by basophil trap accumulation UVB-damaged Supported grants from NIH (F32 AI154787, R01 AI136475, R21 AI169418, AI152444)