{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T13:59:20Z","timestamp":1789567160118,"version":"build-2803163510"},"reference-count":57,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,11,27]],"date-time":"2022-11-27T00:00:00Z","timestamp":1669507200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Although neuronal Toll\u2010like receptors (TLRs) (e.g.,\u00a0TLR2, TLR3, and TLR7) have been implicated in itch sensation, the roles of keratinocyte TLRs in chronic itch are elusive. Herein, we evaluated the roles of keratinocyte TLR2 and TLR7 in chronic itch under dry skin and psoriasis conditions, which was induced by either acetone\u2010ether\u2010water treatment or 5% imiquimod cream in mice, respectively. We found that TLR2 and TLR7 signaling were significantly upregulated in dry skin and psoriatic skin in mice. Chronic itch and epidermal hyperplasia induced by dry skin or psoriasis were comparably reduced in TLR2 and TLR7 knockout mice. In the dry skin model, the enhanced messenger RNA\u00a0(mRNA) expression levels of pruritic CXCL1\/2, IL\u201031, IL\u201033, ST2, IL\u20106, IL\u201017A, TNF\u2010\u03b1, and IFN\u2010\u03b3 were inhibited in TLR2<jats:sup>\u2212\/\u2212<\/jats:sup> mice, while CXCL2, IL\u201031, and IL\u20106 were inhibited in TLR7<jats:sup>\u2212\/\u2212<\/jats:sup> mice. In psoriasis model, the enhanced mRNA expression levels of pruritic CXCL1\/2, IL\u201031, IL\u201033, ST2, IL\u20106, and TNF\u2010\u03b1 were inhibited in TLR2<jats:sup>\u2212\/\u2212<\/jats:sup> mice, while CXCL1\/2, IL\u201031, IL\u201033, ST2, IL\u20106, IL\u201017A, and TNF\u2010\u03b1 were inhibited in TLR7<jats:sup>\u2212\/\u2212<\/jats:sup> mice. Incubation with <jats:italic>Staphylococcus aureus<\/jats:italic> (<jats:italic>S. aureus<\/jats:italic>) peptidoglycan (PGN\u2010SA) (a TLR2 agonist), imiquimod (a TLR7 agonist), and miR142\u20103p (a putative TLR7 agonist) were sufficient to upregulate the expression of pruritic cytokines or chemokines in cultured keratinocyte HaCaT cells. Finally, pharmacological blockade of C\u2010X\u2010C Motif Chemokine Receptor 1\/2 and high mobility group box protein 1 dose\u2010dependently attenuated acute and chronic itch in mice. Together, these results indicate that keratinocyte TLR2 and TLR7 signaling pathways are distinctly involved in the pathogenesis of chronic itch.<\/jats:p>","DOI":"10.1002\/jcp.30923","type":"journal-article","created":{"date-parts":[[2022,11,27]],"date-time":"2022-11-27T20:33:38Z","timestamp":1669581218000},"page":"257-273","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Keratinocyte TLR2 and TLR7 contribute to chronic itch through pruritic cytokines and chemokines in mice"],"prefix":"10.1002","volume":"238","author":[{"given":"Zhi\u2010Hong","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Endocrinology The Second Affiliated Hospital of Soochow University  Suzhou China"},{"name":"Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience Soochow University  Suzhou 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