期刊
出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2019097118
关键词
UV light; neutrophil migration; kidney; inflammation
资金
- NIH [R56 AR073848, T32 AR007108, R01 AR074939, R21 AR075134]
- Institute of Translation Health Sciences Catalyst Awards, University of Washington
Exposure to UV light triggers a neutrophil-dependent injury response in the kidney, leading to subclinical renal inflammation and injury. Neutrophils not only migrate to the skin but also to the kidney post UV light exposure, contributing to the renal induction of inflammation and injury genes. Patients with lupus have blood neutrophils similar to those observed in mice post-UV exposure, suggesting a potential role of these cells in mediating inflammation and injury.
Photosensitivity to ultraviolet (UV) light affects up to similar to 80% of lupus patients. Sunlight exposure can exacerbate local as well as systemic manifestations of lupus, including nephritis, by mechanisms that are poorly understood. Here, we report that acute skin exposure to UV light triggers a neutrophil-dependent injury response in the kidney characterized by upregulated expression of endothelial adhesion molecules as well as inflammatory and injury markers associated with transient proteinuria. We showed that UV light stimulates neutrophil migration not only to the skin but also to the kidney in an IL-17A-dependent manner. Using a photoactivatable lineage tracing approach, we observed that a subset of neutrophils found in the kidney had transited through UV light-exposed skin, suggesting reverse transmigration. Besides being required for the renal induction of genes encoding mediators of inflammation (vcam-1, s100A9, and Il-1b) and injury (lipocalin-2 and kim-1), neutrophils significantly contributed to the kidney type I interferon signature triggered by UV light. Together, these findings demonstrate that neutrophils mediate subclinical renal inflammation and injury following skin exposure to UV light. Of interest, patients with lupus have subpopulations of blood neutrophils and low-density granulocytes with similar phenotypes to reverse transmigrating neutrophils observed in the mice post-UV exposure, suggesting that these cells could have transmigrated from inflamed tissue, such as the skin.
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