{"doi":"10.4049/jimmunol.2200065","title":"ICAM-1 Abundance Is Increased in Pancreatic Islets of Hyperglycemic Female NOD Mice and Is Rapidly Upregulated by NF-κB in Pancreatic β-Cells","abstract":"Type 1 diabetes (T1D) is classified as an autoimmune disease where pancreatic β-cells are specifically targeted by cells of the immune system. The molecular mechanisms underlying this process are not completely understood. Herein, we identified that the Icam1 gene and ICAM-1 protein were selectively elevated in female NOD mice relative to male mice, fitting with the sexual dimorphism of diabetes onset in this key mouse model of T1D. In addition, ICAM-1 abundance was greater in hyperglycemic female NOD mice than in age-matched normoglycemic female NOD mice. Moreover, we discovered that the Icam1 gene was rapidly upregulated in response to IL-1β in mouse, rat, and human islets and in 832/13 rat insulinoma cells. This early temporal genetic regulation requires key components of the NF-κB pathway and was associated with rapid recruitment of the p65 transcriptional subunit of NF-κB to corresponding κB elements within the Icam1 gene promoter. In addition, RNA polymerase II recruitment to the Icam1 gene promoter in response to IL-1β was consistent with p65 occupancy at κB elements, histone chemical modifications, and increased mRNA abundance. Thus, we conclude that β-cells undergo rapid genetic reprogramming by IL-1β to enhance expression of the Icam1 gene and that elevations in ICAM-1 are associated with hyperglycemia in NOD mice. These findings are highly relevant to, and highlight the importance of, pancreatic β-cell communication with the immune system. Collectively, these observations reveal a portion of the complex molecular events associated with onset and progression of T1D.","journal":"The Journal of Immunology","year":2022,"id":277910,"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":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9517,"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":418292,"name":"Susan J. Burke","orcid":"0000-0003-2571-4416","position":1,"is_corresponding":false},{"id":419208,"name":"Heidi M. Batdorf","orcid":null,"position":2,"is_corresponding":false},{"id":418286,"name":"David H. Burk","orcid":"0000-0002-6487-0174","position":3,"is_corresponding":false},{"id":250669,"name":"Sujoy Ghosh","orcid":"0000-0002-7601-165X","position":4,"is_corresponding":false},{"id":720819,"name":"Samuel D. Dupuy","orcid":"0000-0001-8372-0860","position":5,"is_corresponding":false},{"id":418288,"name":"Michael D. Karlstad","orcid":"0000-0002-3190-8738","position":6,"is_corresponding":false},{"id":418284,"name":"J. Jason Collier","orcid":"0000-0003-2817-4152","position":7,"is_corresponding":false},{"id":316544,"name":"Thomas M. Martin","orcid":"0000-0002-1671-6498","position":0,"is_corresponding":true}],"reference_count":64,"raw_metadata":null,"created_at":"2026-07-19T00:28:43.133347Z","pmid":"35851539","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":[]}