{"doi":"10.1038/s41375-021-01158-9","title":"Danger-associated molecular pattern molecules take unexpectedly a central stage in Nlrp3 inflammasome–caspase-1-mediated trafficking of hematopoietic stem/progenitor cells","abstract":"Like their homing after transplantation to bone marrow (BM), the mobilization of hematopoietic stem/progenitor cells (HSPCs) is still not fully understood, and several overlapping pathways are involved. Several years ago our group proposed that sterile inflammation in the BM microenvironment induced by pro-mobilizing agents is a driving force in this process. In favor of our proposal, both complement cascade (ComC)-deficient and Nlrp3 inflammasome-deficient mice are poor G-CSF and AMD3100 mobilizers. It is also known that the Nlrp3 inflammasome mediates its effects by activating caspase-1, which is responsible for proteolytic activation of interleukin-1β (IL-1β) and interleukin-18 (IL-18) and their release from cells along with several danger-associated molecular pattern molecules (DAMPs). We observed in the past that IL-1β and IL-18 independently promote mobilization of HSPCs. In the current work we demonstrated that caspase-1-KO mice are poor mobilizers, and, to our surprise, administration of IL-1β or IL-18, as in the case of Nlrp3-KO animals, does not correct this defect. Moreover, neither Caspase-1-KO nor Nlrp3-KO mice properly activated the ComC to execute the mobilization process. Interestingly, mobilization in these animals and activation of the ComC were both restored after injection of the DAMP cocktail eATP+HGMB1+S100A9, the components of which are normally released from cells in an Nlrp3 inflammasome-caspase-1-dependent manner. In addition, we report that caspase-1-deficient HSPCs show a decrease in migration in response to BM homing factors and engraft more poorly after transplantation. These results for the first time identify caspase-1 as an orchestrator of HSPC trafficking.","journal":"Leukemia","year":2021,"id":169852,"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":28,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9506,"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":280798,"name":"Mateusz Adamiak","orcid":"0000-0002-3228-9588","position":1,"is_corresponding":false},{"id":251377,"name":"Kamila Bujko","orcid":"0000-0002-2205-1154","position":2,"is_corresponding":false},{"id":235300,"name":"Janina Ratajczak","orcid":"0000-0001-8605-8892","position":3,"is_corresponding":false},{"id":280799,"name":"Ahmed Abdel‐Latif","orcid":"0000-0002-8178-7102","position":4,"is_corresponding":false},{"id":240803,"name":"Magda Kucia","orcid":"0000-0002-9110-5048","position":5,"is_corresponding":false},{"id":235299,"name":"Mariusz Z. Ratajczak","orcid":"0000-0002-0071-0198","position":6,"is_corresponding":false},{"id":280797,"name":"Arjun Thapa","orcid":"0000-0002-8555-5720","position":0,"is_corresponding":true}],"reference_count":59,"raw_metadata":null,"created_at":"2026-07-18T23:46:15.560174Z","pmid":"33623143","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":[]}