{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T20:05:54Z","timestamp":1790712354697,"version":"4.1.0"},"reference-count":62,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T00:00:00Z","timestamp":1694736000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81773327"],"award-info":[{"award-number":["81773327"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acad Dermatol Venereol"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Serine metabolism is crucial for tumour oncogenesis and immune responses. S\u2010adenosyl methionine (SAM), a methyl donor, is typically derived from serine\u2010driven one\u2010carbon metabolism. However, the involvement of serine metabolism in psoriatic skin inflammation remains unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To investigate the association between serine metabolism and psoriatic skin inflammation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Clinical samples were collected from patients with psoriasis and the expression of serine biosynthesis enzymes was evaluated. The HaCaT human keratinocyte cell line was transfected with small interfering RNA (siRNA) of key enzyme or treated with inhibitors. RNA sequencing and DNA methylation assays were performed to elucidate the mechanisms underlying serine metabolism\u2010regulated psoriatic keratinocyte inflammation. An imiquimod (IMQ)\u2010induced psoriasis mouse model was established to determine the effect of the SAM administration on psoriatic skin inflammation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The expression of serine synthesis pathway enzymes, including the first rate\u2010limiting enzyme in serine biosynthesis, phosphoglycerate dehydrogenase (PHGDH), was downregulated in the epidermal lesions of patients with psoriasis compared with that in healthy controls. Suppressing PHGDH in keratinocytes promoted the production of proinflammatory cytokines and enrichment of psoriatic\u2010related signalling pathways, including the tumour necrosis factor\u2010alpha (TNF\u2010\u03b1) signalling pathway, interleukin (IL)\u201017 signalling pathway and NF\u2010\u03baB signalling pathway. In particular, PHGDH inhibition markedly promoted the secretion of IL\u20106 in keratinocytes with or without IL\u201017A, IL\u201022, IL\u20101\u03b1, oncostatin M and TNF\u2010\u03b1 (mix) stimulation. Mechanistically, PHGDH inhibition upregulated the expression of IL\u20106 by inhibiting SAM\u2010dependent DNA methylation at the promoter and increasing the binding of myocyte enhancer factor 2A. Furthermore, PHGDH inhibition increased the secretion of IL\u20106 by increasing the activation of NF\u2010\u03baB via SAM inhibition. SAM treatment effectively alleviated IMQ\u2010induced psoriasis\u2010like skin inflammation in mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our study revealed the crucial role of PHGDH in antagonising psoriatic skin inflammation and indicated that targeting serine metabolism may represent a novel therapeutic strategy for treating psoriasis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jdv.19492","type":"journal-article","created":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T01:04:44Z","timestamp":1693962284000},"page":"145-156","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Serine deficiency exacerbates psoriatic skin inflammation by regulating S\u2010adenosyl methionine\u2010dependent<scp>DNA<\/scp>methylation and<scp>NF\u2010\u03baB<\/scp>signalling activation in keratinocytes"],"prefix":"10.1111","volume":"38","author":[{"given":"Qinqin","family":"Meng","sequence":"first","affiliation":[{"name":"Department of Dermatology The Second Affiliated Hospital of Xi'an Jiaotong University Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Dermatology The Second Affiliated Hospital of Xi'an Jiaotong University Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leiqing","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Dermatology The Second Affiliated Hospital of Xi'an Jiaotong University Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhimiao","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Dermatology The Second Affiliated Hospital of Xi'an Jiaotong University Xi'an 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