{"doi":"10.1101/2021.09.11.21263401","title":"Store-Operated Calcium Entry Controls Innate and Adaptive Immune Cell Function in Inflammatory Bowel Disease","abstract":"Abstract Objective Inflammatory bowel disease (IBD) is characterized by dysregulated intestinal immune responses and constitutes a major clinical challenge in need of new treatment modalities to improve patient care. Store-operated Ca 2+ entry (SOCE) is the predominant Ca 2+ influx pathway in T cells and other immune cells, regulating many of their functional properties. It is currently unknown whether the pharmacologic blockade of SOCE represents a suitable drug-target for IBD treatment. Design Using mass and flow cytometry the effects of SOCE inhibition on lamina propria (LP) immune cells of patients with ulcerative colitis (UC) and Crohn’s disease (CD) were investigated. Primary organoid cultures served to study the impact of SOCE inhibition on the function, differentiation and survival of intestinal epithelial cells (IEC). T cell transfer models of colitis were applied to examine how the genetic or pharmacologic ablation of SOCE affects the clinical course of IBD in mice. Results We observed that the LP of IBD patients is characterized by an enrichment of innate lymphoid cells (ILC), CD4 + and CD8 + effector- as well as T regulatory cells producing IL-17 and TNFα. The pharmacologic inhibition of SOCE attenuated the production of pathogenic cytokines including IL-2, IL-4, IL-6, IL-17, TNFα and IFNγ by human colonic T cells and ILC, reduced the production of IL-6 by B cells and the production of IFNγ by myeloid cells, without affecting the viability, differentiation and function of primary IEC. T cell-specific genetic deletion of the SOCE signaling components Orai1 , Stim1 or Stim2 revealed that the magnitude of SOCE correlates with the function of T cells and intestinal inflammation in mice. Moreover, the pharmacologic inhibition of SOCE alleviated the clinical course of colitic mice. Conclusion Our data suggest that SOCE inhibition may serve as a new pharmacologic strategy for treating IBD.","journal":"medRxiv","year":2021,"id":217828,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9522,"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":325421,"name":"Ulrike Kaufmann","orcid":"0000-0003-4317-5794","position":1,"is_corresponding":false},{"id":815116,"name":"Yin‐Hu Wang","orcid":"0000-0002-3637-8852","position":2,"is_corresponding":false},{"id":815117,"name":"Lorenz Gerbeth","orcid":"0000-0001-6638-1959","position":3,"is_corresponding":false},{"id":815703,"name":"A Sand","orcid":null,"position":4,"is_corresponding":false},{"id":815704,"name":"Max Brunkhorst","orcid":null,"position":5,"is_corresponding":false},{"id":815118,"name":"J Ziegler","orcid":"0000-0001-7445-541X","position":6,"is_corresponding":false},{"id":554055,"name":"Chotima Böttcher","orcid":"0000-0002-6226-586X","position":7,"is_corresponding":false},{"id":815119,"name":"Stephan Schlickeiser","orcid":"0000-0003-3142-2890","position":8,"is_corresponding":false},{"id":815120,"name":"Camila Fernández‐Zapata","orcid":"0000-0003-4795-6053","position":9,"is_corresponding":false},{"id":457151,"name":"Kenneth A. Stauderman","orcid":"0000-0002-8090-4549","position":10,"is_corresponding":false},{"id":815121,"name":"Désirée Kunkel","orcid":"0000-0002-0054-955X","position":11,"is_corresponding":false},{"id":815705,"name":"IBDome researchers","orcid":null,"position":12,"is_corresponding":false},{"id":78759,"name":"Britta Siegmund","orcid":"0000-0002-0055-958X","position":13,"is_corresponding":false},{"id":244372,"name":"Stefan Feske","orcid":"0000-0001-5431-8178","position":14,"is_corresponding":false},{"id":78755,"name":"Carl Weidinger","orcid":"0000-0002-9948-0088","position":15,"is_corresponding":false},{"id":815115,"name":"Marilena Letizia","orcid":"0000-0002-8039-9415","position":0,"is_corresponding":true}],"reference_count":55,"raw_metadata":null,"created_at":"2026-07-18T23:53:24.683898Z","pmid":null,"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":[]}