Elevated circulating Th2 but not group 2 innate lymphoid cell responses characterize canine atopic dermatitis.

Simon P Früh, Mridusmita Saikia, Jeremy Eule, Christina A Mazulis, Julia E Miller, Joby M Cowulich, Oyebola O Oyesola, Lauren M Webb, Seth A Peng, Rebecca L Cubitt, Charles G Danko, William H Miller, Elia D Tait Wojno
Author Information
  1. Simon P Früh: Baker Institute for Animal Health and Department of Microbiology and Immunology, Ithaca, NY 14853, USA.
  2. Mridusmita Saikia: Baker Institute for Animal Health and Department of Biomedical Sciences, Ithaca, NY 14853, USA.
  3. Jeremy Eule: Baker Institute for Animal Health and Department of Microbiology and Immunology, Ithaca, NY 14853, USA.
  4. Christina A Mazulis: Section of Dermatology and Department of Clinical Sciences, Cornell University College of Veterinary Medicine, Ithaca, NY 14853, USA.
  5. Julia E Miller: Section of Dermatology and Department of Clinical Sciences, Cornell University College of Veterinary Medicine, Ithaca, NY 14853, USA.
  6. Joby M Cowulich: Section of Dermatology and Department of Clinical Sciences, Cornell University College of Veterinary Medicine, Ithaca, NY 14853, USA.
  7. Oyebola O Oyesola: Baker Institute for Animal Health and Department of Microbiology and Immunology, Ithaca, NY 14853, USA; Department of Immunology, University of Washington, Seattle, WA 98109, USA.
  8. Lauren M Webb: Baker Institute for Animal Health and Department of Microbiology and Immunology, Ithaca, NY 14853, USA; Department of Immunology, University of Washington, Seattle, WA 98109, USA.
  9. Seth A Peng: Baker Institute for Animal Health and Department of Microbiology and Immunology, Ithaca, NY 14853, USA.
  10. Rebecca L Cubitt: Baker Institute for Animal Health and Department of Microbiology and Immunology, Ithaca, NY 14853, USA.
  11. Charles G Danko: Baker Institute for Animal Health and Department of Biomedical Sciences, Ithaca, NY 14853, USA.
  12. William H Miller: Section of Dermatology and Department of Clinical Sciences, Cornell University College of Veterinary Medicine, Ithaca, NY 14853, USA.
  13. Elia D Tait Wojno: Baker Institute for Animal Health and Department of Microbiology and Immunology, Ithaca, NY 14853, USA; Department of Immunology, University of Washington, Seattle, WA 98109, USA. Electronic address: etwojno@uw.edu.

Abstract

Atopic dermatitis (AD) is an allergic skin disease that causes significant morbidity and affects multiple species. AD is highly prevalent in companion dogs, and the clinical management of the disease remains challenging. An improved understanding of the immunologic and genetic pathways that lead to disease could inform the development of novel treatments. In allergic humans and mouse models of AD, the disease is associated with Th2 and group 2 innate lymphoid cell (ILC2) activation that drives type 2 inflammation. Type 2 inflammation also appears to be associated with AD in dogs, but gaps remain in our understanding of how key type 2-associated cell types such as canine Th2 cells and ILC2s contribute to the pathogenesis of canine AD. Here, we describe previously uncharacterized canine ILC2-like cells and Th2 cells ex vivo that produced type 2 cytokines and expressed the transcription factor Gata3. Increased circulating Th2 cells were associated with chronic canine AD. Single-cell RNA sequencing revealed a unique gene expression signature in T cells in dogs with AD. These findings underline the importance of pro-allergic Th2 cells in orchestrating AD and provide new methods and pathways that can inform the development of improved therapies.

Keywords

MeSH Term

Animals
Blood Cells
Dermatitis, Atopic
Dog Diseases
Dogs
Female
Immunity, Innate
Inflammation
Lymphocytes
Male
Sequence Analysis, RNA
Single-Cell Analysis
Th2 Cells