Photosensitivity is central to cutaneous lupus erythematosus and dermatomyositis (DM), but the mechanisms linking UVB exposure to tissue-specific autoimmunity are poorly defined. Using single-cell RNA sequencing, spatial transcriptomics, proteomics, UVB provocation and in vitro modeling, we identify MMP9⁺CD14⁺ myeloid cells as critical mediators of photosensitivity.
These cells expand significantly in lesional skin, produce interferon-β (IFNβ) and colocalize with cytotoxic CD4⁺ T cells at the dermal–epidermal junction. Keratinocytes activate fibroblasts in the superficial dermis, prompting them to release chemokines (CCL2, CCL19, CCL7, CCL8) that recruit MMP9⁺CD14⁺ cells.
In vitro, type I interferon-primed keratinocytes exposed to UVB release cytokines activating dendritic cells, mirroring in vivo responses. UVB irradiation of non-lesional skin of patients with DM rapidly recruits these myeloid cells.
In a clinical proof-of-concept study, anti-type I interferon treatment with anifrolumab prevented UVB-induced myeloid infiltration and reduced photosensitivity. Therefore, targeting MMP9⁺CD14⁺ cells may offer therapeutic potential for managing photosensitive autoimmune skin conditions.
Ultraviolet (UV) light presents a paradox in cutaneous immunology: broadly therapeutic in psoriasis and vitiligo, yet a potent trigger of inflammation in cutaneous lupus erythematosus (CLE) and dermatomyositis (DM).
Nature Immunology published a clinical update in Infectious Disease on 24 Apr 2026.
The item focuses on A spatially coordinated keratinocyte–fibroblast circuit recruits MMP9⁺ myeloid cells to drive type I interferon-driven inflammation in photosensitive autoimmunity.
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