项目编号

PRJCA006797

项目标题

Anatomically distinct fibroblast subsets determine skin autoimmune disease patterns

涉及领域

Medical

数据类型

Transcriptome or Gene expression

物种名称

Homo sapiens
Mus

描述信息

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.

样品范围

Monoisolate

发布日期

2021-10-06

出版信息

PubMed ID	文章标题	杂志名称	Doi	发表年份
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
39190494	CXCL9, CXCL10, and CCL19 synergistically recruit T lymphocytes to skin in lichen planus	JCI Insight	10.1172/jci.insight.179899	2024
40361040	Comprehensive single-cell transcriptomic reveals different destinies of melanocytes and dynamic changes of immune microenvironment in a psychological stress-induced leukoderma and leukotrichia mouse model	Molecular Medicine	10.1186/s10020-025-01236-z	2025
40608219	A Comparative Analysis Dissecting the Immune Landscape of Vitiligo and Melanoma from a single-cell Perspective: Two Sides of the Same Coin?	Inflammation	10.1007/s10753-025-02332-2	2025
40742316	Pan-Cancer Analyses Refine the Single-Cell Portrait of Tumor-Infiltrating Dendritic Cells	Cancer Research	10.1158/0008-5472.CAN-24-3595	2025
39921788	Sirtuin1 Deficiency Could Exacerbate Melanocyte Apoptosis Under Endoplasmic Reticulum Stress	Inflammation	10.1007/s10753-025-02255-y	2025
41438679	Exosomal miR-493-3p Promote the Secretion of CXCL10 by Suppressing Keratinocyte Autophagy in Vitiligo	Clinical, Cosmetic and Investigational Dermatology	10.2147/CCID.S566887	2025
39937331	Mechanism of Ca(2+) overload caused by STIM1/ORAI1 activation of store-operated Ca(2+) entry (SOCE) in hydrogen peroxide-induced mitochondrial damage and apoptosis in human primary melanocytes	Molecular Biology Reports	10.1007/s11033-025-10329-1	2025
	Comprehensive single-cell transcriptomic reveals different destinies of melanocytes and dynamic changes of immune microenvironment in a psychological stress …	Molecular Medicine	10.1186/s10020-025-01236-z	2025
40753527	Nitric oxide induces apoptosis of human primary melanocytes by regulating calcium homeostasis via VDAC1	Molecular and Cellular Biochemistry	10.1007/s11010-025-05361-5	2025
41365874	Early skin seeding regulatory T cells modulate PPARγ-dependent skin pigmentation	Nature Communications	10.1038/s41467-025-66229-2	2025
39300285	SPRR1B+ keratinocytes prime oral mucosa for rapid wound healing via STAT3 activation	Communications Biology	10.1038/s42003-024-06864-5	2024
41498037	Single‐Cell Transcriptomic Analysis Reveals an Inflammatory Antigen‐Presenting Macrophages Subtype Drive Vitiligo Pathogenesis Through STAT1‐Mediated Dual Mechanisms	Mediators of Inflammation	10.1155/mi/8878698	2025
41896475	A Comparative Single-Cell Atlas Reveals Pre-injury Signatures of Superior Healing in Oral Mucosa and Informing a New Paradigm for Wound Management	Functional & Integrative Genomics	10.1007/s10142-026-01862-8	2026
40659088	SIRT7 facilitates ferroptosis resistance of melanocytes via activating the SMAD3-ATF3-GPX4 signaling pathway in vitiligo	Journal of Advanced Research	10.1016/j.jare.2025.07.020	2025

实验材料提供者

Jianmin Chang and Wenhui Wang

项目资金来源

机构	项目类型	授权项目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

提交者

Ting C (chenting@nibs.ac.cn)

提交单位

National Institute of Biological Sciences, Beijing

提交日期

2021-10-06

项目包含数据信息

资源名称	描述
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