Single-cell analysis reveals innate lymphoid cell lineage infidelity in atopic dermatitis.
J Allergy Clin Immunol
; 149(2): 624-639, 2022 02.
Article
in En
| MEDLINE
| ID: mdl-34363841
ABSTRACT
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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Lymphocytes
/
Cell Lineage
/
Single-Cell Analysis
Limits:
Humans
Language:
En
Journal:
J Allergy Clin Immunol
Year:
2022
Document type:
Article