{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T09:24:09Z","timestamp":1790069049067,"version":"4.0.1"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2014,12,1]],"date-time":"2014-12-01T00:00:00Z","timestamp":1417392000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The proprotein convertase subtilisin\/kexin enzymes proteolytically convert immature proproteins into bioactive molecules, and thereby they serve as key regulators of cellular homeostasis. The archetype proprotein convertase subtilisin\/kexin, FURIN, is a direct target gene of the IL-12\/STAT4 pathway and it is upregulated in Th1 cells. We have previously demonstrated that FURIN expression in T cells critically regulates the maintenance of peripheral immune tolerance and the functional maturation of pro\u2013TGF-\u03b21 in vivo, but FURIN\u2019s role in cell-mediated immunity and Th polarization has remained elusive. In this article, we show that T cell\u2013expressed FURIN is essential for host resistance against a prototypic Th1 pathogen, Toxoplasma gondii, and for the generation of pathogen-specific Th1 lymphocytes, including Th1\u2013IL-10 cells. FURIN-deficient Th cells instead show elevated expression of IL-4R subunit \u03b1 on cell surface, sensitized IL-4\/STAT6 signaling, and a propensity to polarize toward the Th2 phenotype. By exploring FURIN-interacting proteins in Jurkat T cells with Strep-Tag purification and mass spectrometry, we further identify an association with a cytoskeleton modifying Ras-related C3 botulinum toxin substrate\/dedicator of cytokinesis 2 protein complex and unravel that FURIN promotes F-actin polymerization, which has previously been shown to downregulate IL-4R subunit \u03b1 cell surface expression and promote Th1 responses. In conclusion, our results demonstrate that in addition to peripheral immune tolerance, T cell\u2013expressed FURIN is also a central regulator of cell-mediated immunity and Th1\/2 cell balance.<\/jats:p>","DOI":"10.4049\/jimmunol.1401629","type":"journal-article","created":{"date-parts":[[2014,10,30]],"date-time":"2014-10-30T03:03:14Z","timestamp":1414638194000},"page":"5470-5479","source":"Crossref","is-referenced-by-count":31,"title":["Proprotein Convertase FURIN Constrains Th2 Differentiation and Is Critical for Host Resistance against <i>Toxoplasma gondii<\/i>"],"prefix":"10.1093","volume":"193","author":[{"given":"Anna","family":"Oksanen","sequence":"first","affiliation":[{"name":"Laboratory of Immunoregulation, BioMediTech, University of Tampere , 33014 Tampere ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saara","family":"Aittom\u00e4ki","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoregulation, BioMediTech, University of Tampere , 33014 Tampere ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dragana","family":"Jankovic","sequence":"additional","affiliation":[{"name":"Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zsuzsanna","family":"Ortutay","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoregulation, BioMediTech, University of Tampere , 33014 Tampere ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kati","family":"Pulkkinen","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoregulation, BioMediTech, University of Tampere , 33014 Tampere ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanna","family":"H\u00e4m\u00e4l\u00e4inen","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoregulation, BioMediTech, University of Tampere , 33014 Tampere ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Rokka","sequence":"additional","affiliation":[{"name":"Turku Centre for Biotechnology, University of Turku and \u00c5bo Akademi University , 20520 Turku ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Garry L","family":"Corthals","sequence":"additional","affiliation":[{"name":"Turku Centre for Biotechnology, University of Turku and \u00c5bo Akademi University , 20520 Turku ,","place":["Finland"]},{"name":"Van\u2019t Hoff Institute for Molecular Sciences, University of Amsterdam , 1090 GD Amsterdam ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy T","family":"Watford","sequence":"additional","affiliation":[{"name":"Lymphocyte Cell Biology Section, Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health , Bethesda, MD 20892"},{"name":"Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia , Athens, GA 30602"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilkka","family":"Junttila","sequence":"additional","affiliation":[{"name":"Fimlab Laboratories, Pirkanmaa Hospital District , 33101 Tampere ,","place":["Finland"]},{"name":"School of Medicine, University of Tampere , 33014 Tampere ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John J","family":"O\u2019Shea","sequence":"additional","affiliation":[{"name":"Lymphocyte Cell Biology Section, Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marko","family":"Pesu","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoregulation, BioMediTech, University of Tampere , 33014 Tampere ,","place":["Finland"]},{"name":"Fimlab Laboratories, Pirkanmaa Hospital District , 33101 Tampere ,","place":["Finland"]},{"name":"Department of Dermatology, Pirkanmaa Hospital District , 33101 Tampere ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,12,1]]},"reference":[{"key":"2025030707491337100_r1","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1126\/science.1178334","article-title":"Mechanisms underlying lineage commitment and plasticity of helper CD4+ T 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