Defining cell type-specific immune responses in a mouse model of allergic contact dermatitis by single-cell transcriptomics

作者：Youxi Liu, Meimei Yin, Xiaoting Mao, Shuai Wu, Shuangping Wei, Shujun Heng, Yichun Yang, Jinwen Huang, Zhuolin Guo, Chuan Li, Chao Ji, Liu Hu, Wenjie Liu, Ling‐juan Zhang · 发表于：eLife · 年份：2024 · DOI：10.7554/elife.94698 · 被引用次数：7 · 研究领域：Contact Dermatitis and Allergies、Dermatology and Skin Diseases、T-cell and B-cell Immunology

Allergic contact dermatitis (ACD), a prevalent inflammatory skin disease, is elicited upon repeated skin contact with protein-reactive chemicals through a complex and poorly characterized cellular network between immune cells and skin resident cells. Here, single-cell transcriptomic analysis of the murine hapten-elicited model of ACD reveals that upon elicitation of ACD, infiltrated CD4 + or CD8 + lymphocytes were primarily the IFNγ-producing type 1 central memory phenotype. In contrast, type 2 cytokines (IL4 and IL13) were dominantly expressed by basophils, IL17A was primarily expressed by δγ T cells, and IL1β was identified as the primary cytokine expressed by activated neutrophils/monocytes and macrophages. Furthermore, analysis of skin resident cells identified a sub-cluster of dermal fibroblasts with preadipocyte signature as a prominent target for IFNγ + lymphocytes and dermal source for key T cell chemokines CXCL9/10. IFNγ treatment shifted dermal fibroblasts from collagen-producing to CXCL9/10-producing, which promoted T cell polarization toward the type-1 phenotype through a CXCR3-dependent mechanism. Furthermore, targeted deletion of Ifngr1 in dermal fibroblasts in mice reduced Cxcl9/10 expression, dermal infiltration of CD8 + T cell, and alleviated ACD inflammation in mice. Finally, we showed that IFNγ + CD8 + T cells and CXCL10-producing dermal fibroblasts co-enriched in the dermis of human ACD skin. Together, our results define the cell type-specific immune respo...