{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:19:14Z","timestamp":1785410354170,"version":"3.56.0"},"posted":{"date-parts":[[2026,4,14]]},"group-title":"Immunology","reference-count":47,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T00:00:00Z","timestamp":1776124800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["R35GM146890"],"award-info":[{"award-number":["R35GM146890"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R03NS144870"],"award-info":[{"award-number":["R03NS144870"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,14]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>Regulatory T cells (Tregs) are essential for maintaining immune homeostasis by suppressing excessive activation of effector T cells. Although several mechanisms of Treg-mediated suppression have been described, the molecular signals that contribute to this regulation remain incompletely understood. WNT signaling, best known for its roles in development and tissue homeostasis, has recently emerged as an important regulator of immune function, but its contribution to Treg-mediated immune suppression is largely unknown.<\/jats:p>\n                <jats:p>\n                  Here, we show that Tregs preferentially express multiple canonical WNT ligands, including WNT2B, WNT3, WNT7B, and WNT10B, compared with conventional CD4\n                  <jats:sup>+<\/jats:sup>\n                  T cells. These WNT proteins were detected intracellularly in Tregs, and WNT2B and WNT3 were actively secreted into culture supernatants. Conventional CD4\n                  <jats:sup>+<\/jats:sup>\n                  T cells expressed Frizzled receptors capable of sensing these ligands. Pharmacological inhibition of canonical WNT signaling using the antagonist mDKK-1 enhanced CD4\n                  <jats:sup>+<\/jats:sup>\n                  T cell activation and proliferation and increased pro-inflammatory cytokine expression, while anti-inflammatory IL-10 remained unchanged.\n                <\/jats:p>\n                <jats:p>\n                  Together, these findings identify Tregs as a source of canonical WNT ligands and suggest that Treg-derived WNT signaling contributes to the suppression of effector CD4\n                  <jats:sup>+<\/jats:sup>\n                  T cell responses. This work reveals a previously underappreciated pathway through which Tregs regulate immune activity and identifies WNT signaling as a potential target for modulating inflammatory immune responses.\n                <\/jats:p>","DOI":"10.64898\/2026.04.12.717050","type":"posted-content","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T06:10:18Z","timestamp":1776233418000},"source":"Crossref","is-referenced-by-count":0,"title":["Canonical WNT Ligands Produced by Regulatory T Cells Restrain Effector CD4\n                  <sup>+<\/sup>\n                  T Cell Responses"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-8599-5007","authenticated-orcid":false,"given":"Kashish","family":"Singh Parihar","sequence":"first","affiliation":[{"name":"Department of Immunology, Cincinnati Children\u2019s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH USA"},{"name":"Department of Molecular and Cellular Biosciences, College of Medicine, University of Cincinnati, Cincinnati, OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6413-2869","authenticated-orcid":false,"given":"Margaret R.","family":"Niemeier","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biosciences, College of Medicine, University of Cincinnati, Cincinnati, OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2945-2580","authenticated-orcid":false,"given":"Igal","family":"Ifergan","sequence":"additional","affiliation":[{"name":"Department of Immunology, Cincinnati Children\u2019s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH USA"},{"name":"Department of Molecular and Cellular Biosciences, College of Medicine, University of Cincinnati, Cincinnati, OH USA"},{"name":"Neuroscience Graduate Program, College of Medicine, University of Cincinnati, Cincinnati, OH 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