{"doi":"10.3389/fimmu.2021.756548","title":"Partners in Crime: Beta-Cells and Autoimmune Responses Complicit in Type 1 Diabetes Pathogenesis","abstract":"Type 1 diabetes (T1D) is an autoimmune disease characterized by autoreactive T cell-mediated destruction of insulin-producing pancreatic beta-cells. Loss of beta-cells leads to insulin insufficiency and hyperglycemia, with patients eventually requiring lifelong insulin therapy to maintain normal glycemic control. Since T1D has been historically defined as a disease of immune system dysregulation, there has been little focus on the state and response of beta-cells and how they may also contribute to their own demise. Major hurdles to identifying a cure for T1D include a limited understanding of disease etiology and how functional and transcriptional beta-cell heterogeneity may be involved in disease progression. Recent studies indicate that the beta-cell response is not simply a passive aspect of T1D pathogenesis, but rather an interplay between the beta-cell and the immune system actively contributing to disease. Here, we comprehensively review the current literature describing beta-cell vulnerability, heterogeneity, and contributions to pathophysiology of T1D, how these responses are influenced by autoimmunity, and describe pathways that can potentially be exploited to delay T1D.","journal":"Frontiers in Immunology","year":2021,"id":149263,"datarank":0.7091081728068512,"base_score":4.727387818712341,"endowment":4.727387818712341,"self_citation_contribution":0.7091081728068512,"citation_network_contribution":0.0,"self_endowment_contribution":0.7091081728068512,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":112,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9594,"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":634760,"name":"KaLia Burnette","orcid":"0000-0002-6522-9899","position":1,"is_corresponding":false},{"id":310406,"name":"Ronadip R. Banerjee","orcid":"0000-0001-8310-251X","position":2,"is_corresponding":false},{"id":634761,"name":"Chad S. Hunter","orcid":"0000-0002-1644-447X","position":3,"is_corresponding":false},{"id":625374,"name":"Hubert M. Tse","orcid":"0000-0001-5861-7597","position":4,"is_corresponding":false},{"id":634759,"name":"Eliana Toren","orcid":"0000-0002-6827-4521","position":0,"is_corresponding":true}],"reference_count":222,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:42:51.282401Z","pmid":"34691077","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":[]}