Systemic lupus cutaneous photoresponses are characterized by dysregulated epidermal inflammation and inflammatory myeloid cell infiltration

ABSTRACT: For patients with systemic lupus erythematosus (SLE), sun avoidance and sunscreen use are the only preventive therapies for photosensitivity, a process by which exposure to ultraviolet (UV) light triggers cutaneous and systemic flares of disease. Photosensitivity is exceedingly common amongst SLE patients with skin disease, affecting up to 93% of this population. Treatment of skin and systemic disease triggered by the sun can be challenging, and thus there exists a critical need for better therapeutic and preventative strategies. Innovation of targeted therapies for photosensitive skin diseases requires a precise dissection of the cellular players and signaling pathways that contribute to aberrant inflammation following UV exposure. Here, we utilize cutaneous UVB photoexposure of healthy control and SLE patients to provide an atlas of the cutaneous inflammatory response 24 hours after UV exposure in single-cell resolution. We demonstrate that the epidermis is dysregulated in lupus, where epidermal-dermal crosstalk in SLE is dominated by inflammatory keratinocytes following UV exposure in contrast to the healthy control epidermis. In both healthy control and SLE, the downstream consequence of UV exposure is the recruitment of a population of monocyte-derived dendritic cells (moDCs). Though these moDCs are present in relatively equal proportions in SLE and healthy control UV-treated skin, they appear to be derived from distinct circulating monocyte populations. Notably, SLE UV moDCs are characterized by inflammatory and antigen presentation pathways and may represent a precursor to lesional cutaneous lupus CD16+ DCs, identifying a potential link between cutaneous UV responses and cutaneous lupus flare.

ORGANISM(S): Homo sapiens

PROVIDER: GSE289389 | GEO | 2026/09/01

REPOSITORIES: GEO