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| Status |
Public on Aug 20, 2021 |
| Title |
Single-cell analysis reveals innate lymphoid cell lineage infidelity in atopic dermatitis |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Background: Although ample knowledge exists about phenotype and function of cutaneous T lymphocytes, much less is known about the lymphocytic components of the skin’s innate immune system.
Objective: To better understand the biologic role of cutaneous innate lymphoid cells (ILCs), we investigated their phenotypic and molecular features under physiologic (normal human skin [NHS]) and pathologic (lesional skin of patients with atopic dermatitis [AD]) conditions.
Methods: Skin punch biopsies and reduction sheets as well as blood specimens were obtained from either patients with AD or healthy individuals. Cell and/or tissue samples were analyzed by flow cytometry, immunohistochemistry, and single-cell RNA sequencing or subjected to in vitro / ex vivo culture.
Results: Notwithstanding substantial quantitative differences between NHS and AD skin, we found that the vast majority of cutaneous ILCs belong to the CRTH2+ subset and reside in the upper skin layers. Single-cell RNA sequencing of cutaneous ILC-enriched cell samples confirmed the predominance of biologically heterogeneous group 2 ILCs and, for the first time, demonstrated considerable ILC lineage infidelity (coexpression of genes typical of either type 2 [GATA3 and IL13] or type 3/17 [RORC, IL22, and IL26] immunity within individual cells) in lesional AD skin, and to a much lesser extent, in NHS. Similar events were demonstrated in ILCs from skin explant cultures and in vitro expanded ILCs from the peripheral blood.
Conclusion: These findings support the concept that instead of being a stable entity with well-defined components, the skin immune system consists of a network of highly flexible cellular players that are capable of adjusting their function to the needs and challenges of the environment.
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| Overall design |
Investigation of cutaneous ILCs in AD and NHS
NOTE FROM SUBMITTER: Due to patient privacy concerns raw data is not provided.
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| Contributor(s) |
Alkon N, Bauer WM, Krausgruber T, Goh I, Griss J, Nguyen V, Reininger B, Bangert C, Staud C, Brunner PM, Bock C, Haniffa M, Stingl G |
| Citation(s) |
34363841 |
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| Submission date |
Jul 27, 2021 |
| Last update date |
Aug 21, 2021 |
| Contact name |
Natalia Alkon |
| E-mail(s) |
natalia.alkon@meduniwien.ac.at
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| Organization name |
Medical University of Vienna
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| Department |
Department of Dermatology
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| Street address |
Währinger Gürtel 18-20
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| City |
Vienna |
| ZIP/Postal code |
1090 |
| Country |
Austria |
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| Platforms (1) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
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| Samples (7)
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| Relations |
| BioProject |
PRJNA749938 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE180885_RAW.tar |
133.8 Mb |
(http)(custom) |
TAR (of MTX, TSV) |
| Processed data provided as supplementary file |
| Raw data not provided for this record |
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