{"doi":"10.1038/s41598-025-85895-2","title":"Inhibition of skin fibrosis via regulation of Th17/Treg imbalance in systemic sclerosis","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>\n                    Systemic sclerosis (SSc) is an idiopathic systemic connective tissue disorder characterized by fibrosis of the skin and internal organs, with growing interest in the imbalance between Th17 cells and regulatory T cells (Tregs) in the disease’s pathogenesis.\n                    <jats:italic>Heligmosomoides polygyrus</jats:italic>\n                    (Hp), a natural intestinal parasite of mice, is known to induce Tregs in the host. We aimed to investigate the effects of Hp-induced Tregs on bleomycin-induced dermal fibrosis and clarify the role of the Th17/Treg balance in SSc fibrosis. Infection with Hp suppressed the development of bleomycin-induced dermal fibrosis and the infiltration of CD3\n                    <jats:sup>+</jats:sup>\n                    T cells and CD68\n                    <jats:sup>+</jats:sup>\n                    macrophages. Flow cytometric analysis revealed that Hp infection increased Tregs and inhibited the induction of bleomycin-induced Th17 cells. Treg depletion nullified these effects, suggesting that Hp-induced Tregs may prevent bleomycin-induced dermal fibrosis and inflammation. Analysis of the intestinal microbiota showed that bacteria positively correlated with Tregs exhibited a negative correlation with Th17 cells and dermal fibrosis in mice. SSc patients with severe fibrosis displayed a distinct microbiota profile. These results suggest that alterations in the intestinal microbiota may contribute to the Th17/Treg imbalance in SSc and its progression. Enhancing Tregs to regulate the Th17/Treg imbalance may present a promising strategy for suppressing fibrosis in SSc.\n                  </jats:p>","journal":"Scientific Reports","year":2025,"id":650891,"datarank":0.37273599746820013,"base_score":2.4849066497880004,"endowment":2.4849066497880004,"self_citation_contribution":0.37273599746820013,"citation_network_contribution":0.0,"self_endowment_contribution":0.37273599746820013,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"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":1697295,"name":"Chikako Shimokawa","orcid":null,"position":1,"is_corresponding":false},{"id":1371007,"name":"Tamotsu Kato","orcid":"0000-0002-8407-4327","position":2,"is_corresponding":false},{"id":951430,"name":"Akihiko Uchiyama","orcid":"0000-0003-0357-2808","position":3,"is_corresponding":false},{"id":188682,"name":"Yoko Yokoyama","orcid":null,"position":4,"is_corresponding":false},{"id":1087288,"name":"Sachiko Ogino","orcid":null,"position":5,"is_corresponding":false},{"id":1087289,"name":"Ryoko Torii","orcid":null,"position":6,"is_corresponding":false},{"id":821869,"name":"Hajime Hisaeda","orcid":null,"position":7,"is_corresponding":false},{"id":1312682,"name":"Hiroshi Ohno","orcid":"0000-0003-2271-4453","position":8,"is_corresponding":false},{"id":1697308,"name":"Sei-ichiro Motegi","orcid":null,"position":9,"is_corresponding":false},{"id":1087287,"name":"Akiko Sekiguchi","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Inhibition of skin fibrosis via regulation of Th17/Treg imbalance in systemic sclerosis","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>\n                    Systemic sclerosis (SSc) is an idiopathic systemic connective tissue disorder characterized by fibrosis of the skin and internal organs, with growing interest in the imbalance between Th17 cells and regulatory T cells (Tregs) in the disease’s pathogenesis.\n                    <jats:italic>Heligmosomoides polygyrus</jats:italic>\n                    (Hp), a natural intestinal parasite of mice, is known to induce Tregs in the host. We aimed to investigate the effects of Hp-induced Tregs on bleomycin-induced dermal fibrosis and clarify the role of the Th17/Treg balance in SSc fibrosis. Infection with Hp suppressed the development of bleomycin-induced dermal fibrosis and the infiltration of CD3\n                    <jats:sup>+</jats:sup>\n                    T cells and CD68\n                    <jats:sup>+</jats:sup>\n                    macrophages. Flow cytometric analysis revealed that Hp infection increased Tregs and inhibited the induction of bleomycin-induced Th17 cells. Treg depletion nullified these effects, suggesting that Hp-induced Tregs may prevent bleomycin-induced dermal fibrosis and inflammation. Analysis of the intestinal microbiota showed that bacteria positively correlated with Tregs exhibited a negative correlation with Th17 cells and dermal fibrosis in mice. SSc patients with severe fibrosis displayed a distinct microbiota profile. These results suggest that alterations in the intestinal microbiota may contribute to the Th17/Treg imbalance in SSc and its progression. Enhancing Tregs to regulate the Th17/Treg imbalance may present a promising strategy for suppressing fibrosis in SSc.\n                  </jats:p>","is_dataset_classified":null,"base_score":2.4849066497880004,"endowment":2.4849066497880004,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"39789188","pmcid":"PMC11717915","openalex_id":"https://openalex.org/W4406194411","authors":[],"funders":[],"total_grants":0,"fwci":12.4132,"citation_percentile":0.98747875,"influential_citations":0,"citation_trend":[{"year":2025,"count":6},{"year":2026,"count":5}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.nature.com/articles/s41598-025-85895-2.pdf","host_type":"journal"},{"url":"https://www.nature.com/articles/s41598-025-85895-2.pdf","host_type":"publisher"},{"url":"https://www.nature.com/articles/s41598-025-85895-2","host_type":"publisher"},{"url":"https://doi.org/10.1038/s41598-025-85895-2","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/39789188","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/11717915","host_type":"repository"},{"url":"https://doaj.org/article/4e83c3e53d93454288c02311811f9975","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11717915/pdf/41598_2025_Article_85895.pdf","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC11717915","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC11717915?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Dermatology and Skin Diseases","Systemic Sclerosis and Related Diseases","Autoimmune Bullous Skin Diseases","Th17 Cells","T-Lymphocytes, Regulatory","Animals","Scleroderma, Systemic","Fibrosis","Mice","Humans","Bleomycin","Skin","Female","Male","Gastrointestinal Microbiome","Middle Aged","Disease Models, Animal","Adult"],"mesh_terms":["Gastrointestinal Microbiome","Adult","Animals","Bleomycin","Disease Models, Animal","Female","Fibrosis","Humans","Male","Middle Aged","Scleroderma, Systemic","Skin","T-Lymphocytes, Regulatory","Mice","Th17 Cells"],"keywords":["Fibrosis","Bleomycin","Immunology","Inflammation","Pathogenesis","Heligmosomoides polygyrus","Medicine","Immune system","Biology","Pathology","Internal medicine","Microbiota","Systemic Sclerosis","Th17/treg Balance","Heligmosomoides Polygilus"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-10T06:17:25.986742Z","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":[]}