The role of monocytes in UVB-mediated acute skin damage in lupus prone mice

Abstract

Abstract Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disorder with manifestations including skin, joint, and kidney inflammation, that is characterized by production of autoantibodies and sensitivity to ultraviolet (UV) light. The precise mechanisms governing UVB-mediated inflammation are incompletely understood; thus, our study objective is to delineate specific innate immune cell populations contributing to UV-mediated inflammation in lupus-prone mice. To that end, lupus-prone NZM mice, lupus-prone iNZM mice (knockout of alpha chain of type I interferon receptor), and wild type Balb/c mice were treated with 100mJ of UV light daily for 5 days. 24 hours after the final dose, skin samples were harvested from each, and CyTOF analysis was performed, revealing skewing of monocyte and macrophage populations in the skin of lupus prone versus wild type mice in a type I IFN dependent fashion. Subsequently, RNA sequencing was performed on skin samples of UV-irradiated NZM and Balb/c mice, which showed upregulation of known inflammatory monocyte chemoattractant genes in lupus prone mice after UV exposure compared to wild type mice. We further characterized monocyte populations recruited to the skin of NZM, iNZM, and Balb/c mice 24 and 72 hours after a single 300mJ dose of UV light by flow cytometry. Our data show a type I IFN dependent, transient predominance of inflammatory Ly6c hi monocytes in lupus prone versus wild type mice at 24 hours after UV exposure. By 72 hours after UV exposure, proportions of inflammatory monocytes in the lupus prone mice decrease. Future studies will be directed at understanding how these inflammatory monocytes differentiate in the context of a type I IFN rich environment and how this contributes to disease.