{"doi":"10.1093/jimmun/vkaf283.080","title":"ILC2 and TH2 cells serve non redundant roles during anamnestic lung Type 2 immunity 2116","abstract":"Abstract Description Lung anti-helminth immunity elicited by memory type 2 cytokine responses promotes wound healing as well as trapping and elimination of migratory larvae. However, the relative contribution(s) of group 2 innate lymphoid (ILC2s) vs. T-helper 2 (TH2) populations to these effects remain unclear. This study demonstrates that although CD4+ T cells were necessary for pulmonary IL-5/IL-13+ ILC2 accumulation, worm clearance, and tissue repair; their depletion only before secondary challenge did not alter these responses. Conversely, mice deficient in locus control region 1 (LCR1-/-), which selectively lack ILC2s, experience impaired TH2 cell expansion, larval killing, and pulmonary tissue repair, associated with elevated IL-17+ gdT cells and neutrophils upon secondary challenge. Although adoptive transfer of CD4+ T cells into LCR1-/- mice restored larval killing, it failed to promote lung repair or suppress gdT cell-driven neutrophilic inflammation. ILC2s from secondary infected mice were enriched on amphiregulin (Areg) and tryptophan hydroxylase 1 expression, which catalyzes serotonin biosynthesis. Areg treatment rescued parasite clearance and TH2 cells in LCR1-/- mice, whereas serotonin reduced lung haemorrhage and IL-17+ gd T cells in the absence of CD4+ T cells. This work reveals a division of labor between TH2 cells and ILC2s wherein ILC2s and TH2 cells redundantly mediate larval killing and ILC2s alone limit IL-17+gd T cells and promote tissue repair. Funding Sources U01 AI163062-01; RO1 AI123173-05 Topic Categories Microbial, Parasitic, and Fungal Immunology (MPF)","journal":"The Journal of Immunology","year":2025,"id":582507,"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":0.9519,"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":264138,"name":"De’Broski R. Herbert","orcid":"0000-0002-2449-5365","position":1,"is_corresponding":false},{"id":1221804,"name":"Fungai Musaigwa","orcid":"0000-0003-0216-0385","position":2,"is_corresponding":false},{"id":1494580,"name":"Juan Manuel","orcid":null,"position":3,"is_corresponding":false},{"id":1494581,"name":"Inclan Rico","orcid":null,"position":4,"is_corresponding":false},{"id":1494582,"name":"Imani Nicolis","orcid":null,"position":5,"is_corresponding":false},{"id":1173990,"name":"Camila Napuri","orcid":null,"position":6,"is_corresponding":false},{"id":264125,"name":"Li‐Yin Hung","orcid":"0000-0001-7623-1946","position":7,"is_corresponding":false},{"id":247554,"name":"Cailu Lin","orcid":"0000-0001-8909-7758","position":8,"is_corresponding":false},{"id":1494146,"name":"Daniel M. Reed","orcid":"0000-0002-8326-5957","position":9,"is_corresponding":false},{"id":1173615,"name":"Ulrich Membe Femoe","orcid":"0000-0001-8715-152X","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T02:58:55.657290Z","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":[]}