{"doi":"10.1111/cea.70115","title":"Identification of the Cytokines, Growth Factors and Their Receptors Expressed by Human Blood Eosinophils: A Transcriptomics Approach","abstract":"Eosinophils are mainly known to be produced in the bone marrow and in a type-2 (T2) immune environment, in vivo, in many prevalent diseases (e.g., allergies, asthma, atopic dermatitis, chronic sinusitis) as well as other high-burden diseases (e.g., eosinophilic esophagitis, gastritis, enteritis, colitis, life-threatening hypereosinophilic syndromes). Eosinophils are known to have negative effector functions on their surroundings via the release of four granule-stored toxic proteins, MBP (eosinophil major basic protein; PRG2), ECP (eosinophil cationic protein; RNASE3), EDN (eosinophil-derived neurotoxin; RNASE2) and EPX (eosinophil peroxidase). In addition to these toxic proteins, eosinophils release many cytokines and growth factors [1-3], although the list of mediators (i.e., cytokines and growth factors) produced by human mature eosinophils remains largely uncertain. In the present study, using several transcriptomic data sets, we identified what human eosinophils express as cytokines, growth factors, and receptors for such mediators. This analysis allowed us to identify: (1) mediators that eosinophils express for other types of cells and whose protein would act only in a paracrine way (i.e., eosinophils do not express their specific receptors), (2) mediators originating either from eosinophils themselves or exogenously from other cell types that can trigger intracellular signalling in eosinophils (i.e., eosinophils express their complete receptors), and (3) cytokines that eosinophils can bind via their expression of a specific subunit receptor but for which eosinophils lack a second subunit to form a complete receptor. At the University of Lille, blood eosinophils from four healthy donors were isolated from whole blood using MACSxpress Whole Blood human Eosinophil Isolation Kit (Miltenyi Biotech) as well as from participants with uncontrolled severe asthma (n = 21) or patients with refractory severe chronic sinusitis with nasal polyps (CRSwNP) (n = 18) using the EasySep Human Eosinophil Isolation Kit (STEMCELL Technology) as previously described [4]. At the University of Wisconsin-Madison, circulating blood eosinophils were obtained from three allergic donors, and were also purified by negative selection as previously described [5]. Rare visible contaminant cells were typically neutrophils or lymphocytes. Eosinophils were cultured with or without IL-3, IL-5 and GM-CSF for 4, 6 and 24 hours. Detailed RNA-sequencing in Lille and Madison, and depositions in public databases are provided in the Method sections in [4, 5]. Altogether, we found a total of 24 genes known to be genes coding for proteins that are either cytokines or growth factors according to www.uniprot.org and functional annotation in DAVID tools. Among the 24 genes, the expression level of IL16, IL1B, INHBA, OSM, TNFSF13B (BAFF) and VEGFA increased in isolated blood eosinophils from patients with uncontrolled severe asthma compared to healthy individuals, while the expression of IL16, IL18, INHBA, TNFSF13B and TNFSF14 increased in refractory CRSwNP. Thus, further investigations focused on the role of these mediators released by eosinophils in eosinophilic severe asthma, and/or CRSwNP might be of interest. In addition, we found a total of 37 genes expressed and coding for subunits of receptors for cytokines and growth factors. According to the expression of all subunits necessary to form complete and functional receptors, we identified that eosinophils should then be able to respond by intracellular signalling to 19 cytokines/growth factors, among which seven are expressed by eosinophils themselves to be able to act in an autocrine way (GRN, IL-16, IL-18, TGF-ß1, TRAIL, TWEAK and LIGHT; Figure 1A), while 12 mediators can be provided exogenously by other cell types (Figure 1B). Eosinophils also expressed one specific receptor subunit to bind IL-11, IL-12, IL-15, IL-17A, IL-17F, IL-2, IL-25 and IL-6, but lack another receptor subunit required for intracellular signa","journal":"Clinical & Experimental Allergy","year":2025,"id":534142,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9542,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1416287,"name":"Emeline Delaunay","orcid":"0009-0000-9364-9359","position":1,"is_corresponding":false},{"id":1304277,"name":"Arnaud Dendooven","orcid":"0000-0003-4918-2223","position":2,"is_corresponding":false},{"id":371771,"name":"Mats W. Johansson","orcid":"0000-0001-5699-978X","position":3,"is_corresponding":false},{"id":1304279,"name":"F. Dezoteux","orcid":"0000-0001-8930-1042","position":4,"is_corresponding":false},{"id":1304708,"name":"Cécile Chenivesse","orcid":null,"position":5,"is_corresponding":false},{"id":1304280,"name":"G. Mortuaire","orcid":"0000-0002-1592-1625","position":6,"is_corresponding":false},{"id":1214862,"name":"Bertrand Meresse","orcid":"0000-0002-8978-8636","position":7,"is_corresponding":false},{"id":841930,"name":"D. Staumont‐Sallé","orcid":"0000-0002-4780-4212","position":8,"is_corresponding":false},{"id":284645,"name":"Nizar N. Jarjour","orcid":"0000-0003-0170-8927","position":9,"is_corresponding":false},{"id":1304281,"name":"Guillaume Lefèvre","orcid":"0000-0002-9427-7267","position":10,"is_corresponding":false},{"id":110406,"name":"Stéphane Esnault","orcid":"0000-0001-7238-8671","position":0,"is_corresponding":true}],"reference_count":9,"raw_metadata":null,"created_at":"2026-07-19T02:51:43.451278Z","pmid":"41448238","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}