<b>Research data supporting: Skin</b><b><i> </i></b><b><i>Staphylococcus</i></b><b> </b><b>species Differentially Modulate Keratinocyte Cytokine Secretion in Response to UVB</b>

Skin acts as the body’s first line of defence against environmental insults including ultraviolet radiation (UVR) from sunlight and participates in a dialog with its resident skin microbiota, increasingly recognised for its role in shaping and educating the immune responses of the skin in both health and disease. However, how or indeed if it mediates inflammatory responses to sunlight remains unclear. To address this, we investigated the effects of five abundant members of the skin microbiota on cytokine secretion in human primary keratinocytes exposed to a single dose of UVB. Co-culture of primary keratinocytes with a defined 5-species skin commensal community resulted in a non-selective increase in the secretion of innate immune mediators including interleukin-6 (IL-6), independent of UVB exposure. In the absence of UVB, Staphylococcus epidermidis was the dominant species, followed by Staphylococcus hominis within the 5-species community. UVB induced a marked shift in community composition, characterised by increased proliferation of Staphylococcus hominis and reduced Staphylococcus epidermidis abundance, as confirmed by species-specific growth curve analyses. Assessment of species-specific effects using mono-associated host cells revealed S. epidermidis as the predominant contributor to the enhancement of immune mediator secretion. Without the presence of additional community members, UVB amplified S. epidermidis induced cytokine secretion. However, co-culture of S. epidermidis with S. hominis attenuated the heightened inflammatory response to UVB typically associated with S. epidermidis, likely due to the reduced abundance of S. epidermidis following UVB exposure. These findings suggest that our resident skin microbiota may contribute to our inflammatory response to sunlight.皮肤作为机体抵御外界环境损伤的第一道防线，可抵御包括日光中紫外线辐射（ultraviolet radiation, UVR）在内的各类外界刺激，并与其定植的皮肤常驻微生物群（resident skin microbiota）形成互作对话；目前学界已愈发认识到，皮肤微生物群在调节与塑造皮肤健康及疾病状态下的免疫应答中发挥关键作用。然而，皮肤微生物群如何乃至是否介导了机体对日光的炎症应答，目前仍不明确。为解答这一问题，本研究针对暴露于单次剂量中波紫外线（UVB）的人原代角质形成细胞，探究了五种丰度较高的皮肤微生物群成员对其细胞因子分泌的影响。将原代角质形成细胞与一组确定的5种皮肤共生微生物群落共培养后，可观察到包括白细胞介素-6（interleukin-6, IL-6）在内的先天免疫介质的分泌出现非选择性升高，且该效应与UVB暴露无关。在未暴露于UVB的情况下，该5种群落中的优势菌种为表皮葡萄球菌（Staphylococcus epidermidis），其次为霍氏葡萄球菌（Staphylococcus hominis）。UVB暴露可导致群落组成发生显著改变，具体表现为霍氏葡萄球菌的增殖能力增强、表皮葡萄球菌的丰度降低；该结果经物种特异性生长曲线分析得到了验证。通过单一菌种定植宿主细胞的实验评估物种特异性效应后发现，表皮葡萄球菌是增强免疫介质分泌的主要贡献者。在不存在其他群落成员的情况下，UVB可增强表皮葡萄球菌诱导的细胞因子分泌。然而，将表皮葡萄球菌与霍氏葡萄球菌共培养时，可削弱表皮葡萄球菌通常介导的、针对UVB的过度炎症应答；该现象可能源于UVB暴露后表皮葡萄球菌的丰度降低。上述研究结果表明，人体皮肤常驻微生物群可能参与调控机体对日光的炎症应答。