Session Information
Session Type: Abstract Session
Session Time: 2:00PM-3:30PM
Background/Purpose: Ultraviolet light (UV) is a known trigger of cutaneous lupus erythematosus (CLE) flares in systemic lupus erythematosus (SLE) patients, yet cell populations and mechanisms driving UV-induced skin inflammation are poorly understood. In this study, we use single-cell RNA sequencing of skin from healthy control (HC) and SLE patients with a history CLE to identify differences in SLE UV responses that serve as novel mediators of UV injury.
Methods: Seven HC and eight SLE patients were recruited. Biopsies were taken from the upper thigh 24 hours after treatment with 1x minimal erythema dose or from unexposed skin. Cells were processed via 10x pipelines, RNA was sequenced with an average of 10,000 reads per cell, and DEGs were analyzed and compared between HC and SLE patients.
Results: Globally, an increase in type I IFN regulated gene expression was seen in SLE >HC across all cell populations after UV exposure. In the epidermis, UV exposure led to differential gene expression in basal keratinocytes (KCs) where stress responses such as S100 proteins were noted in HC, while chemokines and IFN responses were noted in SLE KC, particularly in spinous and basal inflammatory KCs. Subclustering of fibroblast (FB) populations revealed two subpopulations that increase in proportion following UV exposure in both SLE and HC, identified as IFN-FBs and IL6+ FBs. CellphoneDB analysis revealed significant crosstalk between basal and spinous inflammatory KCs and IFN- and IL6+- FBs in SLE skin, suggesting that basal and spinous inflammatory KCs represent critical mediators of UV signal between the epidermis and dermis in lupus. Analysis of the myeloid compartment did not support an influx of pDCs into the skin at our selected timepoint. However, recruitment of myeloid dendritic cells (moDCs) was robust in both SLE and HC skin. Compared with HC skin, moDCs from SLE patients engaged in greater crosstalk with IL-6- and IFN-fibroblasts through CXCL12, a myeloid chemoattractant. Additionally, lupus moDCs engaged in crosstalk with TREM2+ macrophages, a lupus-specific skin resident population, through chemoattractant proteins.
Conclusion: We thus propose that in SLE skin, UV light induces unique inflammatory keratinocyte responses that educate fibroblasts and resident myeloid cells to recruit inflammatory myeloid dendritic cells, which may contribute to inflammatory cytokine production and downstream adaptive immune cell activation in SLE. Targeting of these pathways may be beneficial for prevention of photosensitive responses.
To cite this abstract in AMA style:
Maz M, Ma F, Gharaee-Kermani M, Victory A, Hurst A, Gudjonsson J, Kahlenberg J. Single-Cell RNA Sequencing Reveals Cellular Drivers of UV-mediated Skin Injury in Cutaneous Lupus [abstract]. Arthritis Rheumatol. 2023; 75 (suppl 9). https://acrabstracts.org/abstract/single-cell-rna-sequencing-reveals-cellular-drivers-of-uv-mediated-skin-injury-in-cutaneous-lupus/. Accessed .« Back to ACR Convergence 2023
ACR Meeting Abstracts - https://acrabstracts.org/abstract/single-cell-rna-sequencing-reveals-cellular-drivers-of-uv-mediated-skin-injury-in-cutaneous-lupus/