Grolleau Chloé, Poisot Thomas, Roux Camille, Perray Laura, Serror Kevin, Alberdi Antonio, How-Kit Alexandre, Bergerat David, Dorgham Karim, Onifarasoaniaina Rachel, Chasset François, Charvet Estelle, Mahevas Thibault, Bozonnat Alizée, Battesti Gilles, Dumont Maëlle, Jachiet Marie, de Masson Adèle, Riller Quentin, Lipin Stanislas, Ulveling Damien, Battistella Maxime, Le Buanec Hélène, Bouaziz Jean-David
Université Paris Cité, INSERM U1342, Institut de Recherche Saint-Louis, Paris, France; Department of Dermatology, Hôpital Saint Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
Université Paris Cité, INSERM U1342, Institut de Recherche Saint-Louis, Paris, France.
J Invest Dermatol. 2025 Jun 9. doi: 10.1016/j.jid.2025.04.043.
Cutaneous lichen planus (LP) is an inflammatory skin disease characterized by an interface dermatitis with lymphocyte infiltration and keratinocyte (KC) cell death. The aim of this study was to investigate the immunopathogenesis of LP and assess the underlying mechanisms that drive the interface dermatitis reaction. We first performed single-cell RNA sequencing on lesional skins from patients with LP compared with healthy control skins and demonstrate that LP skin is imprinted by a type I IFN-rich environment. We highlight unique subsets of inflammatory KCs and fibroblasts highly influenced by type I IFN. We then performed interactome analyses, revealing a close communication between IFN-imbued KCs and immune skin cells. Subsequently, to assess the functional effect of IFN subtypes on the interaction between KCs and CD8 T cells, we performed in vitro models of interface dermatitis. We show that IFN-b sensibilizes KCs to CD8 T-cell-mediated cell death in both allogenic and autologous coculture models. In this study, we illustrate that type I IFN education on skin cells drives the interface dermatitis reaction, thus orchestrating the cross-talk between immune and resident cells in LP skin. Together, our data provide a comprehensive characterization of LP immunopathogenesis and demonstrate the strong involvement of type I IFN in its inflammatory landscape.
皮肤扁平苔藓（LP）是一种炎症性皮肤病，其特征为伴有淋巴细胞浸润和角质形成细胞（KC）死亡的界面性皮炎。本研究的目的是调查LP的免疫发病机制，并评估驱动界面性皮炎反应的潜在机制。我们首先对LP患者的皮损与健康对照皮肤进行了单细胞RNA测序，并证明LP皮肤具有富含I型干扰素的环境特征。我们突出了受I型干扰素高度影响的炎症性KC和成纤维细胞的独特亚群。然后我们进行了相互作用组分析，揭示了富含干扰素的KC与皮肤免疫细胞之间的密切交流。随后，为了评估干扰素亚型对KC与CD8 T细胞相互作用的功能影响，我们构建了界面性皮炎的体外模型。我们发现，在同种异体和自体共培养模型中，IFN-β使KC对CD8 T细胞介导的细胞死亡敏感。在本研究中，我们阐明了皮肤细胞上的I型干扰素调控驱动了界面性皮炎反应，从而协调了LP皮肤中免疫细胞与驻留细胞之间的相互作用。总之，我们的数据全面描述了LP的免疫发病机制，并证明了I型干扰素在其炎症格局中的重要作用。
