{"doi":"10.4049/jimmunol.1901376","title":"The Wnt–β-Catenin–IL-10 Signaling Axis in Intestinal APCs Protects Mice from Colitis-Associated Colon Cancer in Response to Gut Microbiota","abstract":"Abstract Loss of immune tolerance to gut microflora is inextricably linked to chronic intestinal inflammation and colitis-associated colorectal cancer (CAC). The LRP5/6 signaling cascade in APCs contributes to immune homeostasis in the gut, but whether this pathway in APCs protects against CAC is not known. In the current study, using a mouse model of CAC, we show that the LRP5/6–β-catenin–IL-10 signaling axis in intestinal CD11c+ APCs protects mice from CAC by regulating the expression of tumor-promoting inflammatory factors in response to commensal flora. Genetic deletion of LRP5/6 in CD11c+ APCs in mice (LRP5/6ΔCD11c) resulted in enhanced susceptibility to CAC. This is due to a microbiota-dependent increased expression of proinflammatory factors and decreased expression of the immunosuppressive cytokine IL-10. This condition could be improved in LRP5/6ΔCD11c mice by depleting the gut flora, indicating the importance of LRP5/6 in mediating immune tolerance to the gut flora. Moreover, mechanistic studies show that LRP5/6 suppresses the expression of tumor-promoting inflammatory factors in CD11c+ APCs via the β-catenin–IL-10 axis. Accordingly, conditional activation of β-catenin specifically in CD11c+ APCs or in vivo administration of IL-10 protected LRP5/6ΔCD11c mice from CAC by suppressing the expression of inflammatory factors. In summary, in this study, we identify a key role for the LRP5/6–β-catenin–IL-10 signaling pathway in intestinal APCs in resolving chronic intestinal inflammation and protecting against CAC in response to the commensal flora.","journal":"The Journal of Immunology","year":2020,"id":80533,"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":15,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9491,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":418947,"name":"Arulkumaran Shanmugam","orcid":null,"position":1,"is_corresponding":false},{"id":417572,"name":"Punithavathi Ranganathan","orcid":"0000-0002-9058-0859","position":2,"is_corresponding":false},{"id":418948,"name":"Indumathi Manoharan","orcid":null,"position":3,"is_corresponding":false},{"id":345771,"name":"Mohamed S. Hussein","orcid":"0000-0001-9277-713X","position":4,"is_corresponding":false},{"id":390535,"name":"Nikhil Patel","orcid":"0000-0001-9335-0082","position":5,"is_corresponding":false},{"id":417573,"name":"Humberto Sifuentes","orcid":"0000-0002-2345-318X","position":6,"is_corresponding":false},{"id":417574,"name":"Pandelakis A. Koni","orcid":"0000-0002-0892-4764","position":7,"is_corresponding":false},{"id":345772,"name":"Puttur D. Prasad","orcid":"0000-0002-8455-0186","position":8,"is_corresponding":false},{"id":417575,"name":"Muthusamy Thangaraju","orcid":"0000-0003-4202-1638","position":9,"is_corresponding":false},{"id":345773,"name":"Santhakumar Manicassamy","orcid":"0000-0002-2203-3917","position":10,"is_corresponding":false},{"id":418946,"name":"Daniel Swafford","orcid":null,"position":0,"is_corresponding":true}],"reference_count":68,"raw_metadata":null,"created_at":"2026-07-18T21:51:58.988919Z","pmid":"32917787","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":[]}