{"doi":"10.1101/2022.07.19.500438","title":"Group 3 Innate Lymphoid Cells are regulated by WASP in a microbiota-dependent manner","abstract":"Abstract Wiskott-Aldrich syndrome protein (WASP) is a cytoskeletal regulator that is largely restricted to hematopoietic cells. While WASP expression in both lymphocytes and macrophages play a critical role in maintaining intestinal homeostasis, the function of WASP in innate lymphoid cells is unknown. Here we analyzed the role of WASP in the differentiation and function of group 3 innate lymphoid cells (ILC3s). WASP-deficient mice ( Was -/- ) have a marked reduction in ILC3s. Moreover, antimicrobial peptide expression in response to ILC3-derived IL-22 was also reduced in the absence of WASP. In Was -/- mice, we observed a reduction in CCR6 + ILC3s, cells known to restrict immune responses to commensal bacteria. WASP-deficient mice were more susceptible to Citrobacter rodentium , an enteric infection controlled by ILC3s. Interestingly, there was no reduction in ILC3s in Was -/- germ-free mice when compared to WT germ-free mice. ILC3s lacking WASP expression also demonstrated microbially-dependent alterations in gene expression associated with cell migration. Finally, ILC3-like (Rorgt + CD3 - ) cells were reduced in the GI tract of WASP-deficient patients. In conclusion, ILC3-specific expression of WASP is critical for the generation and function of ILC3s in the presence of commensal microflora. Aberrant ILC3 function in the setting of WASP-deficiency may contribute to underlying disease pathogenesis.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":301568,"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":0.9664,"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":749943,"name":"Naresh Singh Redhu","orcid":"0000-0002-0264-9925","position":1,"is_corresponding":false},{"id":992677,"name":"Anubhab Nandy","orcid":"0000-0002-2589-398X","position":2,"is_corresponding":false},{"id":749942,"name":"Yu Hui Kang","orcid":"0000-0001-9081-3969","position":3,"is_corresponding":false},{"id":5784,"name":"Michael Field","orcid":"0000-0002-4003-0568","position":4,"is_corresponding":false},{"id":992678,"name":"Ryan Kelly","orcid":"0000-0001-7546-1176","position":5,"is_corresponding":false},{"id":231799,"name":"Liza Konnikova","orcid":"0000-0003-4804-5497","position":6,"is_corresponding":false},{"id":86846,"name":"Jeremy A. Goettel","orcid":"0000-0002-0749-2357","position":7,"is_corresponding":false},{"id":749940,"name":"Amy M. Tsou","orcid":"0000-0002-0222-5057","position":8,"is_corresponding":false},{"id":5793,"name":"Bruce Horwitz","orcid":"0000-0002-8123-8728","position":9,"is_corresponding":false},{"id":5798,"name":"Scott B. Snapper","orcid":"0000-0003-0267-4247","position":10,"is_corresponding":false},{"id":749941,"name":"Amlan Biswas","orcid":"0000-0003-4299-1001","position":0,"is_corresponding":true}],"reference_count":41,"raw_metadata":null,"created_at":"2026-07-19T00:32:02.193874Z","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":[]}