Single-cell analysis reveals innate lymphoid cell lineage infidelity in atopic dermatitis

Natalia Alkon, Wolfgang M. Bauer, Thomas Krausgruber, Issac Goh, Johannes Griss, Vy Nguyen, Baerbel Reininger, Christine Bangert, Clement Staud, Patrick M. Brunner, Christoph Bock, Muzlifah Haniffa, Georg Stingl

Research output: Contribution to journalArticlepeer-review

57 Scopus citations


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.

Original languageEnglish
Pages (from-to)624-639
Number of pages16
JournalJournal of Allergy and Clinical Immunology
Issue number2
StatePublished - Feb 2022
Externally publishedYes


  • Innate lymphoid cells
  • atopic dermatitis
  • human skin
  • single-cell RNA sequencing


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