{"doi":"10.1126/sciimmunol.adr7057","title":"Inducible protein degradation reveals inflammation-dependent function of the T\n            <sub>reg</sub>\n            cell lineage–defining transcription factor Foxp3","abstract":"<jats:p>\n            Regulatory T cells (T\n            <jats:sub>reg</jats:sub>\n            cells) are immunosuppressive CD4 T cells defined by expression of the transcription factor Foxp3. Genetic loss-of-function mutations in\n            <jats:italic toggle=\"yes\">Foxp3</jats:italic>\n            cause lethal multiorgan autoimmune inflammation resulting from defects in T\n            <jats:sub>reg</jats:sub>\n            cell development and suppressive activity. Whether T\n            <jats:sub>reg</jats:sub>\n            cells are continuously dependent on Foxp3 is still unclear. Here, we leveraged chemically induced protein degradation to show that functionally suppressive T\n            <jats:sub>reg</jats:sub>\n            cells in healthy organs can persist in the near-complete absence of Foxp3 protein for at least 10 days. Conversely, T\n            <jats:sub>reg</jats:sub>\n            cells responding to type 1 inflammation in settings of autoimmunity, viral infection, or cancer were selectively lost upon Foxp3 protein depletion. Acute degradation experiments revealed that Foxp3 acts mostly as a direct transcriptional repressor and modulates responsiveness to cytokine stimulation. This inflammation-dependent requirement for continuous Foxp3 activity enabled induction of a selective antitumor immune response upon systemic Foxp3 depletion, without causing deleterious T cell expansion in healthy organs.\n          </jats:p>","journal":"Science Immunology","year":2025,"id":611979,"datarank":0.48959608908231445,"base_score":2.772588722239781,"endowment":2.772588722239781,"self_citation_contribution":0.41588830833596724,"citation_network_contribution":0.07370778074634719,"self_endowment_contribution":0.41588830833596724,"citer_contribution":0.07370778074634719,"corpus_percentile":null,"corpus_rank":null,"citation_count":15,"citer_count":14,"citers_with_citation_signal":6,"citers_with_endowment":6,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1575431,"name":"Polina Dimitrova","orcid":null,"position":1,"is_corresponding":false},{"id":1575432,"name":"Qiong Sun","orcid":null,"position":2,"is_corresponding":false},{"id":1575433,"name":"Jesse Tennebroek","orcid":null,"position":3,"is_corresponding":false},{"id":904216,"name":"Elisa Marchiori","orcid":"0000-0003-2840-8625","position":4,"is_corresponding":false},{"id":1418056,"name":"Markus Jaritz","orcid":"0000-0002-9326-2047","position":5,"is_corresponding":false},{"id":812338,"name":"René Rauschmeier","orcid":"0000-0002-1073-4046","position":6,"is_corresponding":false},{"id":1575434,"name":"Guillem Estivill","orcid":"0000-0002-8088-3098","position":7,"is_corresponding":false},{"id":1575435,"name":"Anna Obenauf","orcid":"0000-0002-9556-5914","position":8,"is_corresponding":false},{"id":812343,"name":"Meinrad Busslinger","orcid":"0000-0002-9111-9351","position":9,"is_corresponding":false},{"id":273567,"name":"Joris van der Veeken","orcid":"0000-0001-7299-2174","position":10,"is_corresponding":false},{"id":1575430,"name":"Christina Jäger","orcid":"0009-0004-9372-176X","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Inducible protein degradation reveals inflammation-dependent function of the T\n            <sub>reg</sub>\n            cell lineage–defining transcription factor Foxp3","abstract":"<jats:p>\n            Regulatory T cells (T\n            <jats:sub>reg</jats:sub>\n            cells) are immunosuppressive CD4 T cells defined by expression of the transcription factor Foxp3. Genetic loss-of-function mutations in\n            <jats:italic toggle=\"yes\">Foxp3</jats:italic>\n            cause lethal multiorgan autoimmune inflammation resulting from defects in T\n            <jats:sub>reg</jats:sub>\n            cell development and suppressive activity. Whether T\n            <jats:sub>reg</jats:sub>\n            cells are continuously dependent on Foxp3 is still unclear. Here, we leveraged chemically induced protein degradation to show that functionally suppressive T\n            <jats:sub>reg</jats:sub>\n            cells in healthy organs can persist in the near-complete absence of Foxp3 protein for at least 10 days. Conversely, T\n            <jats:sub>reg</jats:sub>\n            cells responding to type 1 inflammation in settings of autoimmunity, viral infection, or cancer were selectively lost upon Foxp3 protein depletion. Acute degradation experiments revealed that Foxp3 acts mostly as a direct transcriptional repressor and modulates responsiveness to cytokine stimulation. This inflammation-dependent requirement for continuous Foxp3 activity enabled induction of a selective antitumor immune response upon systemic Foxp3 depletion, without causing deleterious T cell expansion in healthy organs.\n          </jats:p>","is_dataset_classified":null,"base_score":2.70805020110221,"endowment":2.70805020110221,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"40478934","pmcid":"PMC7617780","openalex_id":"https://openalex.org/W4411085891","authors":[],"funders":[{"funder_name":"European Research Council","grant_id":"101116251","title":"Deconstructing Intestinal Immune Tolerance"},{"funder_name":"European Research Council","grant_id":"101125797","title":"Unlocking a T cell-mediated Immune response in therapy-challenged Tumors"},{"funder_name":"European Commission","grant_id":"955951","title":"Deconstructing the evolution of metastasis"}],"total_grants":3,"fwci":5.6618,"citation_percentile":0.96701001,"influential_citations":0,"citation_trend":[{"year":2025,"count":5},{"year":2026,"count":9}],"oa_status":"green","license":"cc-by","oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/7617780","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/7617780","host_type":"repository"},{"url":"https://www.science.org/doi/pdf/10.1126/sciimmunol.adr7057","host_type":"publisher"},{"url":"https://doi.org/10.1126/sciimmunol.adr7057","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/40478934","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC7617780","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC7617780?pdf=render","host_type":"Europe_PMC"},{"url":"http://dx.doi.org/10.1126/sciimmunol.adr7057","host_type":""},{"url":"http://dx.doi.org/10.1126/SCIIMMUNOL.ADR7057","host_type":""}],"fields_of_study":["Immune Cell Function and Interaction","T-cell and B-cell Immunology","Immunotherapy and Immune Responses","03 medical and health sciences","0302 clinical medicine"],"mesh_terms":["Animals","Inflammation","Mice, Inbred C57BL","Mice, Knockout","Cell Lineage","T-Lymphocytes, Regulatory","Mice","Forkhead Transcription Factors","Proteolysis"],"keywords":["FOXP3","Inflammation","Biology","Transcription factor","Immune system","Cell biology","Autoimmunity","Cancer research","Immunology","T cell","Regulatory T cell","IL-2 receptor","Gene","Genetics","Mice, Inbred C57BL","Mice, Knockout","Mice","Proteolysis","Animals","Forkhead Transcription Factors","Cell Lineage","T-Lymphocytes, Regulatory","Article"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"geo"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-02T00:29:07.058182Z","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":[]}