Abstract
Eosinophils are important in fighting parasitic infections and are implicated in the pathogenesis of asthma and allergy. IL‐5 is a critical regulator of eosinophil development, controlling proliferation, differentiation, and maturation of the lineage. Mice that constitutively express IL‐5 have in excess of 10‐fold more eosinophils in the hematopoietic organs than their wild type (WT) counterparts. We have identified that much of this expansion is in a population of Siglec‐F high eosinophils, which are rare in WT mice. In this study, we assessed transcription in myeloid progenitors, eosinophil precursors, and Siglec‐F medium and Siglec‐F high eosinophils from IL‐5 transgenic mice and in doing so have created a useful resource for eosinophil biologists. We have then utilized these populations to construct an eosinophil trajectory based on gene expression and to identify gene sets that are associated with eosinophil lineage progression. Cell cycle genes were significantly associated with the trajectory, and we experimentally demonstrate an increasing trend toward quiescence along the trajectory. Additionally, we found gene expression changes associated with constitutive IL‐5 signaling in eosinophil progenitors, many of which were not observed in eosinophils.
Highlights
Eosinophils are granulocytes that play a role in the pathogenesis of asthma, atopic dermatitis, and allergy
In IL-5 transgenic (IL5T) mice, both Siglec-F Medium Eosinophils (EoM) and Siglec-F High Eosinophils (EoH) were expanded in all 3 tissues, the effect was more dramatic for EoH cells, which was observed at similar levels to EoM in the bone marrow (BM) and peripheral blood (PB), and was 6-fold more abundant than EoM cells in the Spln
We propose an order for the IL5T eosinophil lineage: a linear trajectory from eosinophil precursor (EoP) to EoM BM to EoH BM to EoH PB
Summary
Eosinophils are granulocytes that play a role in the pathogenesis of asthma, atopic dermatitis, and allergy. Siglec-F possesses an ITIM characteristic of the Siglec family that can mediate inhibitory functions including induction of apoptosis.[9] In mouse models of allergy in which SiglecF ligand has been deleted from bronchial epithelial cells and some immune cells, eosinophil populations are expanded due to reduced apoptosis.[10] Following stimulation in a lung allergy model, Siglec-F expression increases on eosinophils in BM, peripheral blood (PB), and Abbreviations: BM, bone marrow; CMP, common myeloid progenitor; DE, differentially expressed; EoH, Siglec-F High Eosinophils; EoM, Siglec-F Medium Eosinophils; EoP, eosinophil precursor; EPX, eosinophil peroxidase; GMP, granulocyte-macrophage progenitor; GO, gene ontology; IL-5Rα, IL-5 receptor alpha; IL5T, IL-5 transgenic; PB, peripheral blood; Spln, spleen; WT, wild-type. Subsequent statistical tests and graphs were generated with Prism (GraphPad Software)
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