{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T06:59:55Z","timestamp":1785308395188,"version":"3.55.0"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T00:00:00Z","timestamp":1778544000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Regulatory T cells (Tregs) within the tumor microenvironment (TME) exhibit functional heterogeneity, including a Foxp3\n                    <jats:sup>+<\/jats:sup>\n                    T-bet\n                    <jats:sup>+<\/jats:sup>\n                    subset known as Th1-type Treg (Th1-Treg) cells that exert potent immunosuppressive activity. Although IFN-\u03b3 signaling is essential for Th1-Treg differentiation, the cellular source of IFN-\u03b3 in tumors has remained unclear. Here, we reveal that Treg cells themselves are one source of IFN-\u03b3, which enhances the Th1-Treg induction. Treg-derived IFN-\u03b3 acts in an autocrine manner to stabilize T-bet expression and maintain the Th1-Treg phenotype, while Arg1\n                    <jats:sup>+<\/jats:sup>\n                    tumor-associated macrophage (TAM)\u2013derived platelet factor 4 (PF4) amplifies this loop by inducing\n                    <jats:italic>Ifng<\/jats:italic>\n                    transcription in Tregs. Conditional deletion of\n                    <jats:italic>Ifng<\/jats:italic>\n                    in Foxp3\n                    <jats:sup>+<\/jats:sup>\n                    cells impaired Th1-Treg differentiation both in tumors and in the spleen, indicating that Treg-derived IFN-\u03b3 contributes to Th1-Treg maintenance at local and systemic levels. Moreover, Treg-derived IFN-\u03b3 similarly promoted Th1-Treg generation during experimental autoimmune encephalomyelitis, suggesting its role in type 1 inflammatory environments. Together, these findings reveal that Treg-derived IFN-\u03b3 contributes to a positive feedback circuit, acting in concert with other IFN-\u03b3 sources and TAM-derived PF4 to sustain Th1-Treg differentiation and accumulation in tumors, thereby reinforcing immunosuppression.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1756194","type":"journal-article","created":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T05:45:04Z","timestamp":1778564704000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Treg-derived IFN-\u03b3 supports the differentiation of Th1-Treg in tumor immunity and autoimmunity"],"prefix":"10.3389","volume":"17","author":[{"given":"Ayumi","family":"Kuratani","sequence":"first","affiliation":[{"name":"Department of Immunoparasitology, Research Institute for Microbial Diseases, Osaka University","place":["Suita, Osaka, Japan"]},{"name":"Laboratory of Immunoparasitology, World Premier International Immunology Frontier Research Center, Osaka University","place":["Suita, Osaka, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaaki","family":"Okamoto","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease Control, Faculty of Medicine, Oita University","place":["Oita, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sekar","family":"Arumsari","sequence":"additional","affiliation":[{"name":"Department of Immunoparasitology, Research Institute for Microbial Diseases, Osaka University","place":["Suita, Osaka, Japan"]},{"name":"Laboratory of Immunoparasitology, World Premier International Immunology Frontier Research Center, Osaka University","place":["Suita, Osaka, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease Control, Faculty of Medicine, Oita University","place":["Oita, Japan"]},{"name":"Division of Pathophysiology, Research Center for GLOBAL and LOCAL Infectious Diseases, Oita University","place":["Oita, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miwa","family":"Sasai","sequence":"additional","affiliation":[{"name":"Department of Immunoparasitology, Research Institute for Microbial Diseases, Osaka University","place":["Suita, Osaka, Japan"]},{"name":"Laboratory of Immunoparasitology, World Premier International Immunology Frontier Research Center, Osaka University","place":["Suita, Osaka, Japan"]},{"name":"Department of Immunoparasitology, Center for Infectious Disease Education and Research, Osaka University","place":["Suita, Osaka, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Immunoparasitology, Research Institute for Microbial Diseases, Osaka University","place":["Suita, Osaka, Japan"]},{"name":"Laboratory of Immunoparasitology, World Premier International Immunology Frontier Research Center, Osaka University","place":["Suita, Osaka, Japan"]},{"name":"Department of Immunoparasitology, Center for Infectious Disease Education and Research, Osaka University","place":["Suita, Osaka, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.05.009","article-title":"Regulatory T cells and immune tolerance","volume":"133","author":"Sakaguchi","year":"2008","journal-title":"Cell"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1428","article-title":"Regulatory T cells prevent catastrophic autoimmunity throughout the lifespan of mice","volume":"8","author":"Kim","year":"2007","journal-title":"Nat 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