{"doi":"10.1101/2024.01.04.574231","title":"Sensory neurons regulate stimulus-dependent humoral immunity","abstract":"Sensory neurons sense pathogenic infiltration, serving to inform immune coordination of host defense. However, sensory neuron-immune interactions have been predominantly shown to drive innate immune responses. Humoral memory, whether protective or destructive, is acquired early in life - as demonstrated by both early exposure to streptococci and allergic disease onset. Our study further defines the role of sensory neuron influence on humoral immunity in the lung. Using a murine model of Streptococcus pneumonia pre-exposure and infection and a model of allergic asthma, we show that sensory neurons are required for B-cell and plasma cell recruitment and antibody production. In response to S. pneumoniae, sensory neuron depletion resulted in a larger bacterial burden, reduced B-cell populations, IgG release and neutrophil stimulation. Conversely, sensory neuron depletion reduced B-cell populations, IgE and asthmatic characteristics during allergen-induced airway inflammation. The sensory neuron neuropeptide released within each model differed. With bacterial infection, vasoactive intestinal polypeptide (VIP) was preferentially released, whereas substance P was released in response to asthma. Administration of VIP into sensory neuron-depleted mice suppressed bacterial burden and increased IgG levels, while VIP1R deficiency increased susceptibility to bacterial infection. Sensory neuron-depleted mice treated with substance P increased IgE and asthma, while substance P genetic ablation resulted in blunted IgE, similar to sensory neuron-depleted asthmatic mice. These data demonstrate that the immunogen differentially stimulates sensory neurons to release specific neuropeptides which specifically target B-cells. Targeting sensory neurons may provide an alternate treatment pathway for diseases involved with insufficient and/or aggravated humoral immunity.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":485830,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9512,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":665544,"name":"Fengli Zhu","orcid":null,"position":1,"is_corresponding":false},{"id":1103971,"name":"Antoine Millet","orcid":"0000-0001-6195-608X","position":2,"is_corresponding":false},{"id":314445,"name":"Nicolas Millet","orcid":"0000-0002-4644-7153","position":3,"is_corresponding":false},{"id":1235084,"name":"Patrizia M. Germano","orcid":"0000-0003-0996-3295","position":4,"is_corresponding":false},{"id":278349,"name":"Joseph R. Pisegna","orcid":"0000-0002-5442-2474","position":5,"is_corresponding":false},{"id":241529,"name":"Omid Akbari","orcid":"0000-0002-4359-9725","position":6,"is_corresponding":false},{"id":385678,"name":"Taylor A. Doherty","orcid":"0000-0003-3256-0398","position":7,"is_corresponding":false},{"id":314447,"name":"Marc Swidergall","orcid":"0000-0002-5261-6267","position":8,"is_corresponding":false},{"id":674328,"name":"Nicholas Jendzjowsky","orcid":"0000-0002-4342-1839","position":9,"is_corresponding":false},{"id":815890,"name":"Diane Aguilar","orcid":null,"position":0,"is_corresponding":true}],"reference_count":72,"raw_metadata":null,"created_at":"2026-07-19T02:07:52.536246Z","pmid":"38260709","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":[]}