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

• Published in: Veterinary immunology and immunopathology 2020-03, Vol.221, p.110015, Article 110015
• Main Authors: Früh, Simon P., Saikia, Mridusmita, Eule, Jeremy, Mazulis, Christina A., Miller, Julia E., Cowulich, Joby M., Oyesola, Oyebola O., Webb, Lauren M., Peng, Seth A., Cubitt, Rebecca L., Danko, Charles G., Miller, William H., Tait Wojno, Elia D.
• Format: Article
• Language: English
• Subjects: Atopic dermatitis; Canine allergy; Genetic and immunologic factors in allergy; Group 2 innate lymphoid cells; T helper type 2 cells; Type 2 inflammation
• ISSN: 0165-2427; 1873-2534
• DOI: 10.1016/j.vetimm.2020.110015

•Canine group 2 innate lymphoid cells (ILC2s) in peripheral blood were identified.•Gata3 is an ex vivo marker for canine Th2 and ILC2 cells.•Chronic canine atopic dermatitis was associated with an increase in Th2 cells in PBMCs.•Single-cell RNA sequencing revealed a unique set of differentially expressed genes in peripheral blood T cells of allergic dogs. 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.