While 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.
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 atopic dermatitis (AD) patients) conditions.
Skin punch-biopsies and reduction sheets as well as blood specimens were obtained from either AD patients or healthy individuals. Cell/tissue samples were analyzed by flow cytometry, immunohistochemistry, and single cell-RNA sequencing (scRNA-seq) or subjected to in vitro / ex vivo culture.
Notwithstanding substantial quantitative differences between NHS and AD, we found that the vast majority of cutaneous ILCs belong to the CRTH2 subset and reside in the upper skin layers. scRNA-seq of cutaneous ILC-enriched cell samples confirmed the predominance of biologically heterogeneous ILC2s and, for the first time, demonstrated considerable ILC lineage infidelity (co-expression of genes typical of either type 2 (GATA3, IL13) or type 3/17 (RORC, IL22, 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.
These findings support the concept that the skin immune system, instead of being a stable entity with well-defined components, consists of a network of highly flexible cellular players, capable of adjusting their function to the needs and challenges of the environment.

Copyright © 2021. Published by Elsevier Inc.