Background/Purpose: Ultraviolet (UV) light is a known trigger of skin and possibly systemic inflammation in systemic lupus erythematosus (SLE) patients. Although type I interferons (IFN) are upregulated in SLE skin after UV exposure, the mechanisms to explain increased UVB-induced inflammation remain unclear. Here, we identified the role of type I IFNs in regulating immune cell activation between wild-type and lupus-prone mice following UVB exposure.

Methods: 10-week old female lupus-prone (NZM2328), wild-type (BALB/c) and iNZM mice (which lack a functional type I IFN receptor on NZM2328 background) were treated on their dorsal skin with 100mJ/cm² of UVB for 5 consecutive days. Following UVB treatment, draining lymph node cell populations were characterized via flow cytometry and suppression assays. Treated skin was examined for changes in expression of type I IFN genes by real-time PCR.

Results: Two weeks following UVB exposure, lupus-prone NZM2328 mice showed an increase in draining lymph node size and expansion of T cell numbers and T cell activation in the draining lymph nodes. B cells were not increased. Neither Balb/c nor iNZM mice demonstrated this change. This T cell activation was preceded by a significant increase in UVB-induced type I IFN expression in the skin of NZM2328 mice compared to BALB/c mice. To explain the rise in T cell activation, T regulatory (T_reg) cells were examined. Following UVB exposure, both BALB/c and iNZM mice demonstrated an increase in activated T_Reg cells in the draining lymph node 24 hours after the fifth UVB treatment; however, this was not seen in NZM2328 mice. In addition, T_regs isolated from NZM2328 mice draining lymph nodes were not functional in a T cell suppression assay. and this was dependent on type I IFNs as Tregs from UVB-treated iNZM demonstrated excellent suppressive capacity, similar to Balb/c mice.

Conclusion: These data suggest that an environment rich in type I IFNs, such as seen in lupus skin, promotes a skewed UVB-mediated T cell response in which activation of T cells is enhanced secondary to a type I IFN-dependent suppression of T_Reg cells. Thus, we propose that type I IFNs promote are important for UVB-induced inflammation and may be an effective target for prevention of UVB-mediated flares.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/ultraviolet-light-induces-increased-t-cell-activation-in-lupus-prone-mice-via-type-i-interferon-dependent-inhibition-of-t-regulatory-cells/