Achachi Amine, Vocanson Marc, Bastien Philippe, Péguet-Navarro Josette, Grande Sophie, Goujon Catherine, Breton Lionel, Castiel-Higounenc Isabelle, Nicolas Jean-François, Gueniche Audrey
CIRI, Centre de Recherche en Infectiologie, Universite de Lyon, Lyon, France; INSERM, U1111, Lyon, France.
L'Oréal Research and Innovation, Aulnay sous bois, France.
J Invest Dermatol. 2015 Aug;135(8):2058-2067. doi: 10.1038/jid.2015.118. Epub 2015 Mar 25.
UVR causes skin injury and inflammation, resulting in impaired immune function and increased skin cancer risk. Langerhans cells (LCs), the immune sentinels of the epidermis, are depleted for several days following a single UVR exposure and can be reconstituted from circulating monocytes. However, the differentiation pathways leading to the recovery of a normal pool of LCs is still unclear. To study the dynamic changes in human skin with UV injury, we exposed a cohort of 29 healthy human volunteers to a clinically relevant dose of UVR and analyzed sequential epidermal biopsies for changes in leukocyte and dendritic cell (DC) subsets. UV-induced depletion of CD1a(high) LC was compensated by sequential appearance of various epidermal leukocytes. CD14(+) monocytes were recruited as early as D1 post exposure, followed by recruitment of two inflammatory DC subsets that may represent precursors of LCs. These CD1a(low) CD207(-) and the heretofore unknown CD1a(low) CD207(+) DCs appeared at day 1 and day 4 post UVR, respectively, and were endowed with T-cell-activating properties similar to those of LCs. We conclude that recruitment of monocytes and inflammatory DCs appear as a physiological response of the epidermis in order to repair UVR-induced LC depletion associated with immune suppression.
紫外线辐射(UVR)会导致皮肤损伤和炎症,进而损害免疫功能并增加皮肤癌风险。朗格汉斯细胞(LCs)是表皮的免疫哨兵,单次UVR暴露后会减少数日,且可由循环单核细胞重新补充。然而,导致正常LC库恢复的分化途径仍不清楚。为了研究紫外线损伤后人体皮肤的动态变化,我们让29名健康人类志愿者暴露于临床相关剂量的UVR,并分析了连续的表皮活检样本中白细胞和树突状细胞(DC)亚群的变化。紫外线诱导的CD1a(高表达)LC减少通过各种表皮白细胞的相继出现得到补偿。CD14(+)单核细胞在暴露后第1天就被招募,随后是两个炎症性DC亚群的招募,它们可能代表LC的前体。这些CD1a(低表达)CD207(-)和此前未知的CD1a(低表达)CD207(+)DC分别在UVR后第1天和第4天出现,并具有与LC相似的激活T细胞的特性。我们得出结论,单核细胞和炎症性DC的招募是表皮的一种生理反应,目的是修复与免疫抑制相关的紫外线诱导的LC减少。