Induction of Type I Interferon-Dependent Activation and Migration of Inflammatory Dendritic Cells to Local Lymph Nodes by UV Light Exposure

Objective: Photosensitivity occurs in ~75% of patients with lupus. Although UV light radiation (UVR) stimulates type I interferon (IFN-I) in the skin, how UVR-induced skin inflammation leads to downstream effects is poorly understood. Tissue inflammation causes dendritic cells (DCs) to migrate from organs to draining lymph nodes (dLN), including a recently identified inflammatory conventional DC subset (inf cDC2) that are potent antigen-presenting cells. To explore links between UVR and the early immune response, we examined DC and lymphocyte subset migration to dLN in normal and lupus-prone mouse strains as well as the role of IFN-I.

Methods: Mice received a single dose of UV (500 mJ/cm) on the dorsal skin. Brachial and inguinal dLN were harvested at one or two days post-UVR. Flow cytometry using the Symphony A3 cytometer and 15-color staining identified myeloid and lymphoid subsets. Statistical significance was determined by Student's t-test.

Results: Higher numbers of CD64+ myeloid cells as well as inf cDC2 were detected in the dLN after UVR in B6 mice, but not in IFN receptor knockout (IFNAR KO) mice. In contrast, Trex1 mutant mice had an exaggerated IFN-I response in the skin and a higher proportion of inf cDC2 in the dLN.

Conclusion: These findings reveal a previously unknown relationship between skin UVR and the migration of the inf cDC2 population to dLN. They highlight the role of IFN-I in this process, and the differences between Trex1 mutant and normal mice suggest that this may be of relevance to lupus.