{"doi":"10.26508/lsa.202000999","title":"iNKT cells coordinate immune pathways to enable engraftment in nonconditioned hosts","abstract":"Invariant natural killer T (iNKT) cells are a conserved population of innate T lymphocytes that interact with key antigen-presenting cells to modulate adaptive T-cell responses in ways that can either promote protective immunity, or limit pathological immune activation. Understanding the immunological networks engaged by iNKT cells to mediate these opposing functions is a key pre-requisite to effectively using iNKT cells for therapeutic applications. Using a human umbilical cord blood xenotransplantation model, we show here that co-transplanted allogeneic CD4 + iNKT cells interact with monocytes and T cells in the graft to coordinate pro-hematopoietic and immunoregulatory pathways. The nexus of iNKT cells, monocytes, and cord blood T cells led to the release of cytokines (IL-3, GM-CSF) that enhance hematopoietic stem and progenitor cell activity, and concurrently induced PGE 2 -mediated suppression of T-cell inflammatory responses that limit hematopoietic stem and progenitor cell engraftment. This resulted in successful long-term hematopoietic engraftment without pretransplant conditioning, including multi-lineage human chimerism and colonization of the spleen by antibody-producing human B cells. These results highlight the potential for using iNKT cellular immunotherapy to improve rates of hematopoietic engraftment independently of pretransplant conditioning.","journal":"Life Science Alliance","year":2021,"id":190981,"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":13,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9509,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":755831,"name":"Nikhila S. Bharadwaj","orcid":"0000-0002-2854-2720","position":1,"is_corresponding":false},{"id":755832,"name":"Elizabeth Bobeck","orcid":"0000-0002-0257-9074","position":2,"is_corresponding":false},{"id":755833,"name":"Courtney E McDougal","orcid":"0000-0003-1607-5931","position":3,"is_corresponding":false},{"id":429551,"name":"Shidong Ma","orcid":null,"position":4,"is_corresponding":false},{"id":467601,"name":"John‐Demian Sauer","orcid":"0000-0001-9367-794X","position":5,"is_corresponding":false},{"id":338813,"name":"Amy W. Hudson","orcid":"0000-0001-9718-6910","position":6,"is_corresponding":false},{"id":338814,"name":"Jenny E. Gumperz","orcid":"0000-0003-1852-2192","position":7,"is_corresponding":false},{"id":338812,"name":"Nicholas J Hess","orcid":"0000-0001-5720-9305","position":0,"is_corresponding":true}],"reference_count":68,"raw_metadata":null,"created_at":"2026-07-18T23:49:31.121780Z","pmid":"34112724","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":[]}