Background/Purpose: Plasmacytoid dendritic cells (pDCs) are highly specialized cells of the innate immune system that secrete very high levels of interferon alpha (IFN-a) following nucleic acid ligand mediated activation of the Toll-like receptors (TLRs) 7 and 9. Although the presence of large numbers of pDC in the skin of patients with cutaneous lupus and exacerbation of cutaneous lupus by UVB exposure suggests a causal relationship, a direct link is difficult to prove. In mice, pDC have been observed in the skin following virus infections as well as following injury by tape stripping but studies of UVB are very limited.  Here, we asked whether, and under what conditions, UVB-induced inflammation could recruit pDC and type 1 IFN to the skin. 

Methods: Shaved C57BL/6 (B6) mice were irradiated with UVB with either a single dose of 500 mJ/cm² (acute profile) or with 100 mJ/cm²/day for 5 consecutive days (subacute profile). Serial punch biopsies (6 mm) were obtained at 3, 24, and 72 hrs following UVB exposure.  Skin samples were examined for mRNA expression by quantitative PCR of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and Type 1 stimulated genes (MX1, ISG15, ISG20).  mRNA fold change was calculated against non-irradiated control mice.  Skin samples were also evaluated by histology with H&E staining and for the presence of pDCs by staining for the pDC-specific marker Siglec H by immunohistochemistry. The skin was also scored visually in a blinded manner based on degree of erythema and ulceration.

Results: While producing similar levels of IL-1β, TNF-α and IL-6, subacute UVB exposure of B6 mice preferentially induced expression of Type 1 IFN genes when compared to both acute UVB and non-irradiated controls.  IFN-response genes were elevated at each time point with the greatest increase occurring at 72 hours post-UVB.  Subacute UVB exposure also induced transient pDCs infiltration into the dermis and hypodermis that corresponded with Type 1 IFN response genes. To examine the role of UVB-induced Type 1 IFN, subacute UVB-mediated effects in B6 mice were compared to age matched IFNAR KO mice (also on a B6 background).  IFNAR KO mice had increased levels of the pro-inflammatory cytokines, IL-1β and IL-6 at 3 and 24 hrs following UVB compared to B6 mice.  Interestingly, TNF-α levels were similar between B6 and IFNAR KO mice.  Skin scoring for erythema and ulceration showed increased levels of skin damage at 3 and 24 hrs.

Conclusion: Repeated moderate dose of UVB preferentially induced pDC recruitment and Type 1 interferon signature in the skin.  Based on the findings that skin damage and inflammatory cytokines were higher in IFNAR KO compared to control mice following subacute UVB exposure, we conclude that Type 1 IFN plays a protective role in attenuating the acute inflammatory response following repeated UVB exposure. It is likely that repetitive UVB exposure as well as other genetic factors leading to hyperresponsiveness to nucleic acid debris, predispose to lupus.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/ultraviolet-b-induced-plasmacytoid-dendritic-cell-migration-and-type-1-interferon-signaling-in-the-skin/