{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T11:53:27Z","timestamp":1791114807581,"version":"4.1.0"},"reference-count":55,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2009,4,1]],"date-time":"2009-04-01T00:00:00Z","timestamp":1238544000000},"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":[[2009,4,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Immunological tolerance is crucial to avoid autoimmune and inflammatory diseases; however, the mechanisms involved are incompletely understood. To study peripheral tolerance to skin-associated Ags, we generated new transgenic mice expressing a membrane-bound form of OVA in skin under the human keratin 14 (K14) promoter (K14-mOVA mice). In contrast to other transgenic mice expressing similar self-Ags in skin, adoptive transfer of Ag-specific T cells does not induce inflammatory skin disease in our K14-mOVA mice. OVA-specific T cells transferred into K14-mOVA mice are activated in lymphoid tissues, undergo clonal expansion, and eventually acquire effector function. Importantly, these Ag-specific T cells selectively up-regulate expression of E-selectin ligand in cutaneous lymph nodes but not in mesenteric lymph nodes and spleen, demonstrating that expression of endogenous self-Ags in skin dictates imprinting of skin tissue homing in vivo. However, an additional inflammatory signal, here induced by tape stripping, is required in K14-mOVA mice to induce T cell migration to skin and development of inflammatory skin disease. Depletion of regulatory CD4+CD25+ T cells did not provoke homing of transferred T cells to skin under steady-state conditions, indicating that these cells are not the key regulators for inhibiting T cell homing in K14-mOVA mice. Both skin-derived and lymph node-resident CD8\u03b1+ dendritic cells are responsible for Ag presentation in vivo and induce tolerance to skin Ags, as we show by selective depletion of langerin+ and CD11c+ dendritic cells. Taken together, controlled skin homing of T cells is critical for the maintenance of peripheral immune tolerance to epidermal self-Ags.<\/jats:p>","DOI":"10.4049\/jimmunol.0803628","type":"journal-article","created":{"date-parts":[[2009,4,2]],"date-time":"2009-04-02T20:38:25Z","timestamp":1238704705000},"page":"4665-4674","source":"Crossref","is-referenced-by-count":23,"title":["Maintenance of Peripheral Tolerance through Controlled Tissue Homing of Antigen-Specific T Cells in K14-mOVA Mice"],"prefix":"10.1093","volume":"182","author":[{"given":"Teresa","family":"Bianchi","sequence":"first","affiliation":[{"name":"Department of Dermatology, Brigham and Women\u2019s Hospital and Harvard Medical School , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura B","family":"Pincus","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Brigham and Women\u2019s Hospital and Harvard Medical School , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc-Andr\u00e9","family":"Wurbel","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Brigham and Women\u2019s Hospital and Harvard Medical School , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin E","family":"Rich","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Brigham and Women\u2019s Hospital and Harvard Medical School , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas S","family":"Kupper","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Brigham and Women\u2019s Hospital and Harvard Medical School , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert C","family":"Fuhlbrigge","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Brigham and Women\u2019s Hospital and Harvard Medical School , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne","family":"Boes","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Brigham and Women\u2019s Hospital and Harvard Medical School , Boston, MA 02115"},{"name":"Department of Pediatric Immunology, University Medical Center Utrecht, Wilhelmina Children\u2019s Hospital , Utrecht,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,4,15]]},"reference":[{"key":"2025032622401737300_R1","first-page":"211","article-title":"Immune surveillance in the skin: mechanisms and clinical consequences.","volume-title":"Nat. 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