{"doi":"10.1111/j.1365-2567.2006.02326.x","title":"Histamine and prostaglandin E<sub>2</sub>up‐regulate the production of Th2‐attracting chemokines (CCL17 and CCL22) and down‐regulate IFN‐γ‐induced CXCL10 production by immature human dendritic cells","abstract":"<jats:title>Summary</jats:title><jats:p>Effector memory T helper 2 (Th2) cells that accumulate in target organs (i.e. skin or bronchial mucosa) have a central role in the pathogenesis of allergic disorders. To date, the factors that selectively trigger local production of Th2‐attracting chemokines remain poorly understood. In mucosa, at the sites of allergen entry, immature dendritic cells (DC) are in close contact with mast cells. Histamine and prostaglandin E<jats:sub>2</jats:sub>(PGE<jats:sub>2</jats:sub>) are two mediators released by allergen‐activated mast cells that favour the polarization of maturing DC into Th2‐polarizing cells. We analysed here the effects of histamine and PGE<jats:sub>2</jats:sub>on the prototypic, Th2‐(CCL17, CCL22) versus Th1‐(CXCL10) chemokine production by human DC. We report that histamine and PGE<jats:sub>2</jats:sub>dose‐dependently up‐regulate CCL17 and CCL22 by monocyte‐derived immature DC. These effects were potentiated by tumour necrosis factor‐α, still observed in the presence of the Th1‐cytokine interferon‐γ (IFN‐γ) and abolished by the immunomodulatory cytokine interleukin‐10. In addition, histamine and PGE<jats:sub>2</jats:sub>down‐regulated IFN‐γ‐induced CXCL10 production by monocyte‐derived DC. These properties of histamine and PGE<jats:sub>2</jats:sub>were observed at the transcriptional level and were mediated mainly through H2 receptors for histamine and through EP2 and EP4 receptors for PGE<jats:sub>2</jats:sub>. Finally, histamine and PGE<jats:sub>2</jats:sub>also up‐regulated CCL17 and CCL22 and decreased IFN‐γ‐induced CXCL10 production by purified human myeloid DC. In conclusion, these data show that, in addition to polarizing DC into mature cells that promote naïve T‐cell differentiation into Th2 cells, histamine and PGE<jats:sub>2</jats:sub>may act on immature DC to trigger local Th2 cell recruitment through a selective control of Th1/Th2‐attracting chemokine production, thereby contributing to maintain a microenvironment favourable to persistent immunoglobulin E synthesis.</jats:p>","journal":"Immunology","year":2006,"id":637800,"datarank":0.6907755278982138,"base_score":4.605170185988092,"endowment":4.605170185988092,"self_citation_contribution":0.6907755278982138,"citation_network_contribution":0.0,"self_endowment_contribution":0.6907755278982138,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":99,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1656236,"name":"Gersende Caron","orcid":null,"position":1,"is_corresponding":false},{"id":688216,"name":"Simon Blanchard","orcid":"0000-0002-7953-0455","position":2,"is_corresponding":false},{"id":1656238,"name":"Isabelle Frémaux","orcid":null,"position":3,"is_corresponding":false},{"id":776024,"name":"Dorothée Duluc","orcid":"0000-0002-7252-9072","position":4,"is_corresponding":false},{"id":1656243,"name":"Yves Delneste","orcid":null,"position":5,"is_corresponding":false},{"id":1656246,"name":"Alain Chevailler","orcid":null,"position":6,"is_corresponding":false},{"id":1656248,"name":"Pascale Jeannin","orcid":null,"position":7,"is_corresponding":false},{"id":1656234,"name":"Anne McIlroy","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Histamine and prostaglandin E<sub>2</sub>up‐regulate the production of Th2‐attracting chemokines (CCL17 and CCL22) and down‐regulate IFN‐γ‐induced CXCL10 production by immature human dendritic cells","abstract":"<jats:title>Summary</jats:title><jats:p>Effector memory T helper 2 (Th2) cells that accumulate in target organs (i.e. skin or bronchial mucosa) have a central role in the pathogenesis of allergic disorders. To date, the factors that selectively trigger local production of Th2‐attracting chemokines remain poorly understood. In mucosa, at the sites of allergen entry, immature dendritic cells (DC) are in close contact with mast cells. Histamine and prostaglandin E<jats:sub>2</jats:sub>(PGE<jats:sub>2</jats:sub>) are two mediators released by allergen‐activated mast cells that favour the polarization of maturing DC into Th2‐polarizing cells. We analysed here the effects of histamine and PGE<jats:sub>2</jats:sub>on the prototypic, Th2‐(CCL17, CCL22) versus Th1‐(CXCL10) chemokine production by human DC. We report that histamine and PGE<jats:sub>2</jats:sub>dose‐dependently up‐regulate CCL17 and CCL22 by monocyte‐derived immature DC. These effects were potentiated by tumour necrosis factor‐α, still observed in the presence of the Th1‐cytokine interferon‐γ (IFN‐γ) and abolished by the immunomodulatory cytokine interleukin‐10. In addition, histamine and PGE<jats:sub>2</jats:sub>down‐regulated IFN‐γ‐induced CXCL10 production by monocyte‐derived DC. These properties of histamine and PGE<jats:sub>2</jats:sub>were observed at the transcriptional level and were mediated mainly through H2 receptors for histamine and through EP2 and EP4 receptors for PGE<jats:sub>2</jats:sub>. Finally, histamine and PGE<jats:sub>2</jats:sub>also up‐regulated CCL17 and CCL22 and decreased IFN‐γ‐induced CXCL10 production by purified human myeloid DC. In conclusion, these data show that, in addition to polarizing DC into mature cells that promote naïve T‐cell differentiation into Th2 cells, histamine and PGE<jats:sub>2</jats:sub>may act on immature DC to trigger local Th2 cell recruitment through a selective control of Th1/Th2‐attracting chemokine production, thereby contributing to maintain a microenvironment favourable to persistent immunoglobulin E synthesis.</jats:p>","is_dataset_classified":null,"base_score":4.605170185988092,"endowment":4.605170185988092,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"16556265","pmcid":null,"openalex_id":"https://openalex.org/W2030375512","authors":[],"funders":[],"total_grants":0,"fwci":4.0437,"citation_percentile":0.93908026,"influential_citations":0,"citation_trend":[{"year":2012,"count":13},{"year":2013,"count":8},{"year":2014,"count":3},{"year":2015,"count":2},{"year":2016,"count":4},{"year":2017,"count":4},{"year":2018,"count":2},{"year":2019,"count":3},{"year":2020,"count":3},{"year":2021,"count":5},{"year":2022,"count":8},{"year":2023,"count":1},{"year":2024,"count":4},{"year":2025,"count":1},{"year":2026,"count":2}],"oa_status":"green","license":"http://onlinelibrary.wiley.com/termsAndConditions#vor","oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/1782249","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/1782249","host_type":"repository"},{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2Fj.1365-2567.2006.02326.x","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2567.2006.02326.x","host_type":"publisher"},{"url":"https://doi.org/10.1111/j.1365-2567.2006.02326.x","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/16556265","host_type":"repository"},{"url":"https://inserm.hal.science/inserm-03374710","host_type":"repository"}],"fields_of_study":["Asthma and respiratory diseases","Allergic Rhinitis and Sensitization","Mast cells and histamine","Cells, Cultured","Chemokine CCL17","Chemokine CCL22","Chemokine CXCL10","Chemokines","Chemokines, CC","Chemokines, CXC","Dendritic Cells","Down-Regulation","Drug Synergism","Histamine","Humans","Interferon-gamma","Prostaglandins E","RNA, Messenger","Receptors, Histamine H2","Receptors, Prostaglandin E","Receptors, Prostaglandin E, EP2 Subtype","Receptors, Prostaglandin E, EP4 Subtype","Reverse Transcriptase Polymerase Chain Reaction","Th2 Cells","Tumor Necrosis Factor-alpha","Up-Regulation"],"mesh_terms":["Cells, Cultured","Dendritic Cells","Drug Synergism","Histamine","Humans","Interferon-gamma","Prostaglandins E","Receptors, Histamine H2","RNA, Messenger","Tumor Necrosis Factor-alpha","Down-Regulation","Up-Regulation","Receptors, Prostaglandin E","Th2 Cells","Chemokines","Chemokines, CC","Chemokines, CXC","Reverse Transcriptase Polymerase Chain Reaction","Chemokine CXCL10","Chemokine CCL17","Chemokine CCL22","Receptors, Prostaglandin E, EP2 Subtype","Receptors, Prostaglandin E, EP4 Subtype"],"keywords":["CXCL10","Histamine","CCL22","CCL17","Chemokine","Cell biology","Histamine H4 receptor","CXCR3","Cytokine","Immunology","CXCL11","Prostaglandin D2","Chemistry","Histamine H2 receptor","Biology","Cancer research","Receptor","Prostaglandin","Chemokine receptor","Inflammation","Endocrinology","Biochemistry"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T19:33:03.385671Z","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":[]}