084 UVB induces prolonged T cell activation in lupus-prone mice via type I IFN inhibition of T regulatory cells

Abstract

Many patients with systemic lupus erythematosus (SLE) are photosensitive, which is characterized by the development of systemic and cutaneous symptoms following minimal sun exposure. While type I IFNs are increased in SLE skin after ultraviolet light (UV) exposure, the mechanisms to explain photosensitivity remain unclear. In-depth mechanistic studies conducted in wild-type mice show induction of a suppressive immune response to UVB, but how this applies to lupus-prone mice is unknown. This study explores the question of how activation of the adaptive immune system differs between wild-type mice vs. lupus-prone mice following UVB exposure, and how type I IFNs contribute to this difference. In order to examine UVB responses, 10-week old female lupus-prone (NZM2328), wild-type (BALB/c) and iNZM mice (lack type I IFN receptor on NZM background) were treated on their dorsal skin with 100mJ/cm2 of UVB for 5 consecutive days. No differences in the skin injury process (skin thickness) were noted between the mouse strains. Notably, however, only the NZM2328 mice showed an increase in draining lymph node size and T cell activation 2 weeks post UVB exposure. Both BALB/c and iNZM mice demonstrated an increase in functional T regulatory (Treg) cells 2 weeks post UVB treatment; this was not seen in NZM2328 mice. These data suggest that sustained UVB-mediated T cell activation is increased in lupus-prone mice in a type I IFN-dependent fashion through suppression of Tregs. Thus, we propose type I IFNs are important to the photosensitive responses in lupus and suggest that targeting type I IFNs could offer potential as a preventative treatment for UVB induced lupus flares.