{"doi":"10.1101/2022.04.14.488379","title":"IL-33 priming and antigenic stimulation synergistically promote the transcription of proinflammatory cytokine and chemokine genes in human skin mast cells","abstract":"Abstract Background Antigenic stimulation through cross-linking the IgE receptor and epithelial cell-derived cytokine IL-33 are potent stimuli of mast cell (MC) activation. Moreover, IL-33 primes a variety of cell types, including MCs to respond more vigorously to external stimuli. However, target genes induced by the combined IL-33 priming and antigenic stimulation have not been investigated in human skin mast cells (HSMCs) in a genome-wide manner. Furthermore, epigenetic changes induced by the combined IL-33 priming and antigenic stimulation have not been evaluated. Results We found that IL-33 priming of HSMCs enhanced their capacity to promote transcriptional synergy of the IL1B and CXCL8 genes by 16- and 3-fold, respectively, in response to combined IL-33 and antigen stimulation compared to without IL-33 priming. We identified the target genes in IL-33-primed HSMCs in response to the combined IL-33 and antigenic stimulation using RNA sequencing (RNA-seq). We found that the majority of genes synergistically upregulated in the IL-33-primed HSMCs in response to the combined IL-33 and antigenic stimulation were predominantly proinflammatory cytokine and chemokine genes. Moreover, the combined IL-33 priming and antigenic stimulation increase chromatin accessibility in the synergy target genes but not synergistically. Transcription factor binding motif analysis revealed more binding sites for NF-κB, AP-1, GABPA, and RAP1 in the induced or increased chromatin accessible regions of the synergy target genes. Conclusions Our study demonstrates that IL-33 priming greatly potentiates MCs’ ability to transcribe proinflammatory cytokine and chemokine genes in response to antigenic stimulation, shining light on how epithelial cell-derived cytokine IL-33 can cause exacerbation of skin MC-mediated allergic inflammation.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":306832,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9581,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":560610,"name":"Yapeng Li","orcid":"0000-0002-9571-0587","position":1,"is_corresponding":false},{"id":1001497,"name":"Xiaoyu Guan","orcid":null,"position":2,"is_corresponding":false},{"id":924915,"name":"Zahraa Mohammed","orcid":"0000-0002-7284-0100","position":3,"is_corresponding":false},{"id":457805,"name":"Gregorio Gomez","orcid":null,"position":4,"is_corresponding":false},{"id":433777,"name":"Yvonne Hui","orcid":"0000-0001-8012-1838","position":5,"is_corresponding":false},{"id":1001498,"name":"Dianzheng Zhao","orcid":null,"position":6,"is_corresponding":false},{"id":299696,"name":"Carole A. Oskeritzian","orcid":"0000-0003-1380-9186","position":7,"is_corresponding":false},{"id":514788,"name":"Hua Huang","orcid":"0000-0001-7317-8983","position":8,"is_corresponding":false},{"id":514786,"name":"Jun‐Feng Gao","orcid":"0000-0001-5098-5993","position":0,"is_corresponding":true}],"reference_count":66,"raw_metadata":null,"created_at":"2026-07-19T00:32:52.703737Z","pmid":null,"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":[]}