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

Biomaterial provider

Jianmin Chang and Wenhui Wang

Grants

Agency	program	Grant ID
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	-
SAMC1935505	RNA-seq of sample 2 primary human palm fibroblast with IFNG treatment
SAMC1935500	RNA-seq of sample 2 primary human leg fibroblast with IFNG treatment
SAMC1935498	RNA-seq of sample 2 primary human head fibroblast with IFNG treatment
SAMC1935494	RNA-seq of sample 2 primary human hand back fibroblast with IFNG treatment
SAMC1935491	RNA-seq of sample 2 primary human foot back fibroblast with IFNG treatment
SAMC1935487	RNA-seq of sample 2 primary human chest fibroblast with IFNG treatment
SAMC1935484	RNA-seq of sample 2 primary human back fibroblast with IFNG treatment
SAMC1935480	RNA-seq of sample 2 primary human arm fibroblast with IFNG treatment
SAMC1935479	RNA-seq of sample 1 primary human palm fibroblast with IFNG treatment
SAMC1935475	RNA-seq of sample 1 primary human leg fibroblast with IFNG treatment
SAMC1935471	RNA-seq of sample 1 primary human head fibroblast with IFNG treatment
SAMC1935468	RNA-seq of sample 1 primary human hand back fibroblast with IFNG treatment
SAMC1935464	RNA-seq of sample 1 primary human foot back fibroblast with IFNG treatment
SAMC1935462	RNA-seq of sample 1 primary human chest fibroblast with IFNG treatment
SAMC1935458	RNA-seq of sample 1 primary human back fibroblast with IFNG treatment
SAMC1935454	RNA-seq of sample 1 primary human arm fibroblast with IFNG treatment
SAMC1935452	RNA-seq of sample 2 primary human palm fibroblast without IFNG treatment
SAMC1935448	RNA-seq of sample 2 primary human leg fibroblast without IFNG treatment
SAMC1935444	RNA-seq of sample 2 primary human head fibroblast without IFNG treatment
SAMC1935441	RNA-seq of sample 2 primary human hand back fibroblast without IFNG treatment
SAMC1935437	RNA-seq of sample 2 primary human foot back fibroblast without IFNG treatment
SAMC1935433	RNA-seq of sample 2 primary human chest fibroblast without IFNG treatment
SAMC1935430	RNA-seq of sample 2 primary human back fibroblast without IFNG treatment
SAMC1935426	RNA-seq of sample 2 primary human arm fibroblast without IFNG treatment
SAMC1935421	RNA-seq of sample 1 primary human palm fibroblast without IFNG treatment
SAMC1935416	RNA-seq of sample 1 primary human leg fibroblast without IFNG treatment
SAMC1935408	RNA-seq of sample 1 primary human head fibroblast without IFNG treatment
SAMC1935404	RNA-seq of sample 1 primary human hand back fibroblast without IFNG treatment
SAMC1935399	RNA-seq of sample 1 primary human foot back fibroblast without IFNG treatment
SAMC1935392	RNA-seq of sample 1 primary human chest fibroblast without IFNG treatment
SAMC1935388	RNA-seq of sample 1 primary human back fibroblast without IFNG treatment
SAMC1935384	RNA-seq of sample 1 primary human arm fibroblast without IFNG treatment
SAMC463883	RNA-seq of mouse fibroblast from WT mice tail skin with vitiligo induction procedure
SAMC463882	RNA-seq of mouse fibroblast from WT mice tail skin without vitiligo induction procedure
SAMC463881	RNA-seq of mouse fibroblast from IFNGR1KO mice tail skin with vitiligo induction procedure
SAMC463880	RNA-seq of mouse CD8+ T cell from WT mice tail skin with vitiligo induction procedure
SAMC463879	RNA-seq of mouse CD8+ T cell from WT mice spleen with vitiligo induction procedure
SAMC463878	RNA-seq of mouse CD8+ T cell from IFNGR1KO mice tail skin with vitiligo induction procedure
GSA (1)	-
CRA005141	mouse model data of anatomically distinct fibroblast subsets determine skin autoimmune disease patterns