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Neutrophils Mediate Kidney Inflammation Following Acute Skin Exposure to UVB Light
bioRxiv - Immunology Pub Date : 2020-05-28 , DOI: 10.1101/2020.05.25.115204
Sladjana Skopelja-Gardner , Joyce Tai , Xizhang Sun , Lena Tanaka , James A. Kuchenbecker , Jessica M. Snyder , Paul Kubes , Tomas Mustelin , Keith B. Elkon

Photosensitivity to ultraviolet (UV) light affects up to ~80% of lupus patients and can exacerbate local skin disease as well as systemic disease, including lupus nephritis. While neutrophils have been implicated in local tissue injury in lupus in response to immune complex deposition, whether and how they play a role in photosensitivity induced systemic disease is unknown. Here, we show that following skin exposure to UV light, neutrophils migrate not only to the skin, but also to the kidney, in an IL-17A-dependent manner. Kidney infiltrating neutrophils produced reactive oxygen species and their presence was associated with upregulation of endothelial adhesion molecules and inflammatory cytokines as well as the induction of kidney injury markers, including transient proteinuria. Neutrophils were responsible for inflammation and renal injury as demonstrated by experiments that inhibited neutrophil mobilization. Exploiting a mouse model containing photoactivatable immune cells, we observed that a subset of neutrophils found in the kidney had transited through UV light-exposed skin suggesting reverse transmigration. These findings demonstrate that neutrophils mediate transient kidney injury following skin exposure to UV light and, coupled with observations identifying similar neutrophil phenotypes in human lupus, could provide a mechanistic link to explain sun-induced systemic lupus flares.

中文翻译:

急性皮肤暴露于UVB光后,中性粒细胞介导肾脏炎症

对紫外线(UV)的光敏性会影响约80%的狼疮患者,并可能加剧局部皮肤疾病以及全身性疾病,包括狼疮肾炎。尽管嗜中性粒细胞参与了针对免疫复合物沉积的狼疮局部组织损伤,但尚不清楚它们是否以及如何在光敏性诱导的全身性疾病中发挥作用。在这里,我们表明在皮肤暴露于紫外线后,嗜中性粒细胞不仅以IL-17A依赖性方式迁移到皮肤,而且迁移到肾脏。肾浸润的中性粒细胞产生活性氧,它们的存在与内皮粘附分子和炎性细胞因子的上调以及肾脏损伤标记物的诱导有关,包括短暂性蛋白尿。如抑制嗜中性白细胞动员的实验所证明,嗜中性白细胞负责炎症和肾损伤。利用含有光活化免疫细胞的小鼠模型,我们观察到在肾脏中发现的中性粒细胞子集已经通过暴露于紫外线的皮肤转移,这表明逆向迁移。这些发现表明,嗜中性粒细胞在皮肤暴露于紫外线下后介导短暂的肾脏损伤,再加上观察发现人类狼疮中类似的嗜中性粒细胞表型,可以提供机制联系来解释太阳引起的系统性红斑狼疮。我们观察到在肾脏中发现的中性粒细胞子集已经通过暴露于紫外线的皮肤转移,这表明逆向迁移。这些发现表明,嗜中性粒细胞在皮肤暴露于紫外线下后介导短暂的肾脏损伤,再加上观察到人类狼疮中类似的嗜中性粒细胞表型的观察结果,可以提供机制联系来解释太阳引起的系统性狼疮发作。我们观察到在肾脏中发现的中性粒细胞子集已经通过暴露于紫外线的皮肤转移,这表明逆向迁移。这些发现表明,嗜中性粒细胞在皮肤暴露于紫外线下后介导短暂的肾脏损伤,再加上观察到人类狼疮中类似的嗜中性粒细胞表型的观察结果,可以提供机制联系来解释太阳引起的系统性狼疮发作。
更新日期:2020-05-28
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