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
Baker Institute for Animal Health and Department of Microbiology and Immunology, Ithaca, NY 14853, USA.
Baker Institute for Animal Health and Department of Biomedical Sciences, Ithaca, NY 14853, USA.
Vet Immunol Immunopathol. 2020 Mar;221:110015. doi: 10.1016/j.vetimm.2020.110015. Epub 2020 Jan 24.
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.
特应性皮炎（AD）是一种过敏性皮肤病，会导致严重发病，并影响多个物种。AD在伴侣犬中高度流行，该疾病的临床管理仍然具有挑战性。对导致该疾病的免疫和遗传途径的深入了解可为新型治疗方法的开发提供依据。在患有AD的人类和小鼠模型中，该疾病与驱动2型炎症的Th2细胞和2型固有淋巴细胞（ILC2）激活有关。2型炎症似乎也与犬类的AD有关，但我们对关键的2型相关细胞类型（如犬类Th2细胞和ILC2）如何促成犬类AD发病机制的理解仍存在空白。在此，我们描述了以前未被鉴定的犬类ILC2样细胞和体外Th2细胞，它们产生2型细胞因子并表达转录因子Gata3。循环中Th2细胞增多与慢性犬类AD有关。单细胞RNA测序揭示了患有AD的犬类T细胞中独特的基因表达特征。这些发现强调了促过敏性Th2细胞在协调AD中的重要性，并提供了可指导改进治疗方法开发的新方法和途径。
