{"doi":"10.3389/frtra.2023.1149334","title":"Type I interferons augment regulatory T cell polarization in concert with ancillary cytokine signals","abstract":"In the transplant community, research efforts exploring endogenous alternatives to inducing tolerogenic allo-specific immune responses are much needed. In this regard, CD4 + FoxP3 + regulatory T cells (T regs ) are appealing candidates due to their intrinsic natural immunosuppressive qualities. To date, various homeostatic factors that dictate T reg survival and fitness have been elucidated, particularly the non-redundant roles of antigenic CD3 ζ /T-cell-receptor, co-stimulatory CD28, and cytokine interleukin (IL-)2 dependent signaling. Many of the additional biological signals that affect T regs remain to be elucidated, however, especially in the transplant context. Previously, we demonstrated an unexpected link between type I interferons (IFNs) and T regs in models of multiple myeloma (MM)—where MM plasmacytes escaped immunological surveillance by enhancing type I IFN signaling and precipitating upregulated T reg responses that could be overturned with specific knockdown of type I IFN signaling. Here, we elaborated on these findings by assessing the role of type I IFN signaling (IFN-α and -β) on T reg homeostasis within an alloimmune context. Specifically, we studied the induction of T regs from naïve CD4 T cells. Using in vitro and in vivo models of murine skin allotransplantation, we found that type I IFN indeed spatiotemporally enhanced the polarization of naïve CD4 T cells into FoxP3 + T regs . Notably, however, this effect was not independent of, and rather co-dependent on, ancillary cytokine signals including IL-2. These findings provide evidence for the relevance of type I IFN pathway in modulating FoxP3 + T reg responses and, by extension, stipulate an additional means of facilitating T reg fitness via type I IFNs.","journal":"Frontiers in Transplantation","year":2023,"id":365426,"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":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.952,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":282630,"name":"Hazim Allos","orcid":"0000-0001-7335-9098","position":1,"is_corresponding":false},{"id":386323,"name":"Jenelle M. Safadi","orcid":null,"position":2,"is_corresponding":false},{"id":282628,"name":"Ina Sulkaj","orcid":"0000-0002-2494-8942","position":3,"is_corresponding":false},{"id":614252,"name":"Jan‐Stephan Sanders","orcid":"0000-0002-0904-3969","position":4,"is_corresponding":false},{"id":247122,"name":"Paolo Cravedi","orcid":"0000-0001-7837-0923","position":5,"is_corresponding":false},{"id":104601,"name":"Irene M. Ghobrial","orcid":"0000-0001-7361-3092","position":6,"is_corresponding":false},{"id":247121,"name":"Stefan P. Berger","orcid":"0000-0003-2228-4676","position":7,"is_corresponding":false},{"id":282643,"name":"Jamil Azzi","orcid":"0000-0002-6909-4645","position":8,"is_corresponding":false},{"id":282627,"name":"Siawosh K. Eskandari","orcid":"0000-0003-4867-4170","position":0,"is_corresponding":true}],"reference_count":21,"raw_metadata":null,"created_at":"2026-07-19T01:14:46.760245Z","pmid":"38993887","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":[]}