Accession PRJCA006797
Title Anatomically distinct fibroblast subsets determine skin autoimmune disease patterns
Relevance Medical
Data types Transcriptome or Gene expression
Organisms Homo sapiens
Mus
Description The skin serves as a physical barrier and an immunological interface that protects the body from the external environment1-3. The aberrant activation of immune cell activity can provoke common skin autoimmune diseases such as psoriasis and vitiligo, which are often characterized by bilateral symmetric lesions at preferred anatomic regions of the body4-9. Understanding what orchestrates patterned cutaneous immune cell activities is necessary for developing effective treatments for these diseases. Here, we identify subsets of dermal fibroblasts responsible for driving patterned autoimmune activity in skin using a robust vitiligo mouse model based on activation of endogenous auto-reactive CD8+ T cells targeting epidermal melanocytes. Through a combination of single-cell transcriptome analysis of patient skin samples, genetic analysis of cell-type-specific knockouts, and engraftment experiments, we find that among multiple IFN-γ-responsive cell types in vitiligo skin, dermal fibroblasts are required to recruit and activate CD8+ cytotoxic T cells through secreted chemokines. Anatomically distinct human dermal fibroblasts exhibit intrinsic differences in chemokine expression in response to IFN-γ. In the mouse model, regional IFN-γ-resistant fibroblasts determine the autoimmune depigmentation pattern in skin. Our study identifies anatomically distinct fibroblasts with permissive or repressive IFN-γ responses as the key driving force that defines body level lesion patterns in vitiligo, and pinpoints mesenchymal subpopulations as novel therapeutic targets for treating autoimmune diseases.
Sample scope Monoisolate
Release date 2021-10-06
Publication
PubMed ID Article title Journal name DOI Year
34912121 Anatomically distinct fibroblast subsets determine skin autoimmune patterns Nature 10.1038/s41586-021-04221-8 2022
Identification and validation of RNA-binding protein SLC3A2 regulates melanocyte ferroptosis in vitiligo by integrated analysis of single-cell and bulk RNA-sequencing Research Square 10.21203/rs.3.rs-3285784/v1 2023
38438962 Identification and validation of RNA-binding protein SLC3A2 regulates melanocyte ferroptosis in vitiligo by integrated analysis of single-cell and bulk RNA-sequencing BMC Genomics 10.1186/s12864-024-10147-y 2024
35962439 Evidence of pyroptosis and ferroptosis extensively involved in autoimmune diseases at the single-cell transcriptome level Journal of Translational Medicine 10.1186/s12967-022-03566-6 2022
A consensus single-cell transcriptomic atlas of dermal fibroblast heterogeneity bioRxiv 10.1101/2024.09.05.611379 2024
Biomaterial provider Jianmin Chang and Wenhui Wang
Grants
Agency program Grant ID Grant title
Ministry of Science and Technology of the People's Republic of China (MOST) National Key Technologies R&D Program 2017YFA0103500
Ministry of Science and Technology of the People's Republic of China (MOST) National Basic Research Program of China (973 Program) 2012CB518700
Ministry of Science and Technology of the People's Republic of China (MOST) National Basic Research Program of China (973 Program) 2014CB849602
Beijing Natural Science Foundation Beijing Municipal Natural Science Foundation 7172192
Submitter Ting C (chenting@nibs.ac.cn)
Organization National Institute of Biological Sciences, Beijing
Submission date 2021-10-06

Project Data

Resource name Description
BioSample (38)  show -
GSA (1) -
CRA005141 mouse model data of anatomically distinct fibroblast subsets determine skin autoimmune disease patterns