Eosinophilic esophagitis (EoE) is a chronic, food antigen-driven, type 2 immune-mediated disease of the esophagus characterized by eosinophil-predominant mucosal inflammation, epithelial remodeling, and subepithelial fibrosis. Although patient biopsies have established the EoE transcriptome and identified key cellular and molecular mediators, biopsy-based research is inherently correlative and cannot resolve causal disease mechanisms, temporal disease progression or the functional hierarchy of immune cell interactions. Thus, animal models are indispensable tools for addressing these limitations. In this Review, we examine the landscape of experimental EoE models. We assess the capacity of each model to recapitulate key disease features including lamina propria and intraepithelial eosinophilia, subepithelial fibrosis, basal cell hyperplasia, epithelial barrier dysfunction, and angiogenesis. We further map these models to human EoE transcriptomic overlap and disease endotype relevance. Across this analysis, we highlight mechanistic insights that were obtained from these models including the eosinophil-independence of IL-13-driven esophageal remodeling, the respective roles of thymic stromal lymphopoietin and IL-33, and the critical role of epithelial-expressed IL-13Rα1. We further highlight the profibrotic functions of amphiregulin-producing T helper 2 cells and colony-stimulating factor 1-dependent macrophages. We discuss the anatomical, genetic and functional limitations of current models and outline directions for the next generation of EoE preclinical systems.

Myeloid cells play key roles in innate and adaptive immunity. Studying their development and function helps reveal new roles and pathogenic mechanisms of related diseases. Zebrafish, a classical model organism, offers various advantages for studying myeloid cell biology. In this review, we focus on recent advances in myeloid cell development and function using the zebrafish model. The pattern and regulation of myelopoiesis and related disorders, including congenital myeloid cell insufficiency and myeloid malignancies, have been revealed, along with related drugs. Regarding function, we highlight myeloid cells, especially macrophages, in homeostasis and regeneration. The bidirectional interactions between myeloid cells and pathogens in zebrafish also provide valuable insights into the mechanisms of infectious diseases. In summary, we highlight the unique contributions of the zebrafish model, demonstrate its complementary roles in basic research and clinical applications relative to mammalian systems, and look forward to more exciting discoveries using this model in the future.

Monocytes consist of several subsets, which differ in their phenotype and functional capacity. This heterogeneity was first shown in man, and later evidenced in other species. Here, we review the current knowledge on the phenotype and functionality of monocyte populations in species of veterinary interest, in comparison to man. The increasing availability of reagents for leukocyte phenotypic analyses, along with the growing application of -omic technologies, are enabling a better characterization of these subsets, and facilitating comparisons across species. The review demonstrates that classical, intermediate, and non-classical monocytes can be defined in pig, cattle, sheep, camel, buffalo, horse, and dog. However, more phenotypic, functional and transcriptomic studies are needed in some species to establish an accurate correspondence. A better understanding of shared and species-specific features of these monocyte subsets will pave the way for translational research on strategies selectively targeting these cells to treat different pathological conditions, including infectious, inflammatory and malignant diseases.

Monocytes consist of several subsets, which differ in their phenotype and functional capacity. This heterogeneity was first shown in man, and later evidenced in other species. Here, we review the current knowledge on the phenotype and functionality of monocyte populations in species of veterinary interest, in comparison to man. The increasing availability of reagents for leukocyte phenotypic analyses, along with the growing application of -omic technologies, are enabling a better characterization of these subsets, and facilitating comparisons across species. The review demonstrates that classical, intermediate, and non-classical monocytes can be defined in pig, cattle, sheep, camel, buffalo, horse, and dog. However, more phenotypic, functional and transcriptomic studies are needed in some species to establish an accurate correspondence. A better understanding of shared and species-specific features of these monocyte subsets will pave the way for translational research on strategies selectively targeting these cells to treat different pathological conditions, including infectious, inflammatory and malignant diseases.

Eosinophilic esophagitis (EoE) is a chronic, food antigen-driven, type 2 immune-mediated disease of the esophagus characterized by eosinophil-predominant mucosal inflammation, epithelial remodeling, and subepithelial fibrosis. Although patient biopsies have established the EoE transcriptome and identified key cellular and molecular mediators, biopsy-based research is inherently correlative and cannot resolve causal disease mechanisms, temporal disease progression or the functional hierarchy of immune cell interactions. Thus, animal models are indispensable tools for addressing these limitations. In this Review, we examine the landscape of experimental EoE models. We assess the capacity of each model to recapitulate key disease features including lamina propria and intraepithelial eosinophilia, subepithelial fibrosis, basal cell hyperplasia, epithelial barrier dysfunction, and angiogenesis. We further map these models to human EoE transcriptomic overlap and disease endotype relevance. Across this analysis, we highlight mechanistic insights that were obtained from these models including the eosinophil-independence of IL-13-driven esophageal remodeling, the respective roles of thymic stromal lymphopoietin and IL-33, and the critical role of epithelial-expressed IL-13Rα1. We further highlight the profibrotic functions of amphiregulin-producing T helper 2 cells and colony-stimulating factor 1-dependent macrophages. We discuss the anatomical, genetic and functional limitations of current models and outline directions for the next generation of EoE preclinical systems.

Myeloid cells play key roles in innate and adaptive immunity. Studying their development and function helps reveal new roles and pathogenic mechanisms of related diseases. Zebrafish, a classical model organism, offers various advantages for studying myeloid cell biology. In this review, we focus on recent advances in myeloid cell development and function using the zebrafish model. The pattern and regulation of myelopoiesis and related disorders, including congenital myeloid cell insufficiency and myeloid malignancies, have been revealed, along with related drugs. Regarding function, we highlight myeloid cells, especially macrophages, in homeostasis and regeneration. The bidirectional interactions between myeloid cells and pathogens in zebrafish also provide valuable insights into the mechanisms of infectious diseases. In summary, we highlight the unique contributions of the zebrafish model, demonstrate its complementary roles in basic research and clinical applications relative to mammalian systems, and look forward to more exciting discoveries using this model in the future.