{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T18:57:01Z","timestamp":1773341821394,"version":"3.50.1"},"reference-count":79,"publisher":"AIP Publishing","issue":"2","license":[{"start":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T00:00:00Z","timestamp":1746748800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["pubs.aip.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,6,1]]},"abstract":"<jats:p>The interaction between keratinocytes (KCs) and immune cells is essential in the pathogenesis of psoriasis. Understanding this crosstalk is crucial for developing effective treatment strategies. Recent studies indicate that Rh family C-type glycoprotein (RHCG) enhances cell proliferation and alters cell differentiation; however, its exact pathogenic mechanisms in psoriasis remain unclear. We employed bioinformatics approaches, including spatial transcriptomics analysis, single-cell transcriptomics analysis, and bulk data analysis, to elucidate the biological functions of RHCG. These predictions were validated through ex vivo experiments and analysis of clinical specimens. In psoriatic skin, RHCG protein levels were significantly upregulated, with an expanded expression area. Notably, RHCG expression was induced under hypoxic conditions. Furthermore, the upregulation of RHCG enhanced the expression of KC markers S100 Calcium Binding Protein A family (S100A) and Keratin 17 (KRT17), while decreasing Keratin 1 (KRT1) expression. Additionally, RHCG overexpression increased the secretion of C-X-C motif chemokine ligand 14 (CXCL14) from KCs, which subsequently activated dendritic cells. Importantly, treatment with secukinumab effectively ameliorated psoriasis by downregulating RHCG expression and inhibiting associated signaling pathways, whereas glucocorticoid and methotrexate treatments resulted in elevated RHCG expression. These findings indicate that RHCG plays a significant role in hypoxia-induced cellular crosstalk and suggest that RHCG-associated signaling may contribute to the superior efficacy of biological agents compared to conventional hormonal and immunosuppressive therapies.<\/jats:p>","DOI":"10.1063\/5.0250742","type":"journal-article","created":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T10:40:21Z","timestamp":1746787221000},"update-policy":"https:\/\/doi.org\/10.1063\/aip-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["Hypoxia-induced RHCG as a key regulator in psoriasis and its modulation by secukinumab"],"prefix":"10.1063","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3283-8858","authenticated-orcid":false,"given":"Shun","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Dermatology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine 1 , Nanjing, Jiangsu 210029,","place":["People's Republic of China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4589-7802","authenticated-orcid":false,"given":"Qian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine 2 , Zhangjiagang, 215600 Jiangsu,","place":["People's Republic of China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5062-555X","authenticated-orcid":false,"given":"Yuan-jie","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine 3 , Nanjing, Jiangsu 210029,","place":["China"]},{"name":"No. 1 Clinical Medical College, Nanjing University of Chinese Medicine 4 , Nanjing, Jiangsu 210023,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3394-1830","authenticated-orcid":false,"given":"Yun-yao","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine 1 , Nanjing, Jiangsu 210029,","place":["People's Republic of China"]},{"name":"No. 1 Clinical Medical College, Nanjing University of Chinese Medicine 4 , Nanjing, Jiangsu 210023,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5694-1139","authenticated-orcid":false,"given":"Cong","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine 1 , Nanjing, Jiangsu 210029,","place":["People's Republic of China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2186-9720","authenticated-orcid":false,"given":"Hui","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine 2 , Zhangjiagang, 215600 Jiangsu,","place":["People's Republic of China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2299-681X","authenticated-orcid":false,"given":"Jia","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine 1 , Nanjing, Jiangsu 210029,","place":["People's Republic of China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"317","published-online":{"date-parts":[[2025,5,9]]},"reference":[{"key":"2025050906401766200_c1","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1016\/S0140-6736(14)61909-7","article-title":"Psoriasis","volume":"386","year":"2015","journal-title":"Lancet"},{"key":"2025050906401766200_c2","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1016\/S0140-6736(07)61128-3","article-title":"Pathogenesis and clinical features of psoriasis","volume":"370","year":"2007","journal-title":"Lancet"},{"key":"2025050906401766200_c3","doi-asserted-by":"publisher","first-page":"1475","DOI":"10.3390\/ijms20061475","article-title":"Psoriasis pathogenesis and treatment","volume":"20","year":"2019","journal-title":"Int. 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