{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T06:47:13Z","timestamp":1775026033609,"version":"3.50.1"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100001582","name":"Dermatology Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001582","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100019401","name":"Hidradenitis Suppurativa Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100019401","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Hidradenitis suppurativa (HS) is a chronic, heterogeneous inflammatory skin disorder with limited therapeutic options. The immune checkpoint receptor TIGIT is emerging as a regulator of chronic inflammation, yet its role in HS remains unknown. Here, we investigated TIGIT and its ligands in HS using tissue profiling, transcriptomics, and an ex vivo functional explant model. A tissue microarray containing 52 HS, 9 ruptured follicular cysts, and 4 normal skin samples demonstrated significantly increased TIGIT expression in HS lesions. In contrast, the TIGIT ligand PVRL3 was significantly decreased in HS, a finding also observed in a publicly available RNA-seq dataset. Because TIGIT suppresses inflammation only when adequately engaged by its ligands, reduced PVRL3 may impair inhibitory checkpoint signaling in HS. To test whether TIGIT engagement could suppress HS inflammation, we developed an ex vivo explant model using freshly obtained HS lesional tissue. The system was validated using triamcinolone, a corticosteroid, which consistently reduced IL-6 production. Treatment with a TIGIT agonist antibody significantly reduced IL-6 by 72 hours. These findings provide the first functional evidence that TIGIT activation attenuates inflammatory pathways in HS, supporting TIGIT agonism as a potential therapeutic strategy.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1761782","type":"journal-article","created":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T04:53:57Z","timestamp":1775019237000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["TIGIT agonism as a therapeutic strategy to suppress inflammation in hidradenitis suppurativa"],"prefix":"10.3389","volume":"17","author":[{"given":"Michal","family":"Kidacki","sequence":"first","affiliation":[{"name":"Department of Dermatology, Yale School of Medicine","place":["New Haven, CT, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anjali","family":"Jaiswal","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Yale School of Medicine","place":["New Haven, CT, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, Yale School of Medicine","place":["New Haven, CT, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samantha","family":"Prince","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, Yale School of Medicine","place":["New Haven, CT, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel","family":"Breidbart","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Yale School of Medicine","place":["New Haven, CT, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henry","family":"Hsia","sequence":"additional","affiliation":[{"name":"Department of Surgery (Plastic and Reconstructive Surgery), Yale School of Medicine","place":["New Haven, CT, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew D.","family":"Vesely","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Yale School of Medicine","place":["New Haven, CT, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lieping","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, Yale School of Medicine","place":["New Haven, CT, United States"]},{"name":"Department of Internal Medicine (Oncology), Yale School of Medicine","place":["New Haven, CT, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1007\/s10227-002-2104-z","article-title":"Clinical practice. 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