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However, the mechanism behind the comorbidity of psoriasis and psychological stress remains unclear. This study established a mouse model of comorbid psoriasis and psychological stress to investigate the impact on skin inflammation and the IL\u201023\/Th17 axis. Chronic restraint stress and imiquimod cream were used to induce psychological stress and psoriasis. Behavioural tests included the open\u2010field test and elevated plus maze, while psoriasis severity was assessed using the Psoriasis Severity Index and histopathology. Flow cytometry measured cDC2 populations in the lesion and spleen, and ELISA quantified levels of key inflammatory factors in serum and lesions. Mice with psoriasis alone showed anxiety symptoms, which were significantly exacerbated in the comorbid group. The comorbid group exhibited more severe lesions, with elevated levels of IL\u201023 and IL\u201017A in both serum and lesions compared to the psoriasis\u2010only group. The number of CD11c<jats:sup>+<\/jats:sup> cDCs in the dermis and the proportion of cDC2s in the lesion and spleen were also significantly higher in the comorbid group. Psychological stress intensifies anxiety symptoms and exacerbates the inflammatory response in the skin and systemic tissues of mice with comorbid psoriasis and psychological stress. This occurs via the overactivation of the IL\u201023\/Th17 inflammatory axis, leading to increased mobilisation of cDC2s and higher levels of inflammatory mediators like IL\u201023 and IL\u201017A, thus chronicling inflammation. These findings enhance our understanding of the mechanisms linking psoriasis and psychological disorders, paving the way for identifying potential therapeutic targets.<\/jats:p><\/jats:sec>","DOI":"10.1111\/exd.70128","type":"journal-article","created":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T03:15:27Z","timestamp":1750389327000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Psychological Stress Overactivates <scp>IL<\/scp>\u201023\/Th17 Inflammatory Axis and Increases <scp>cDC2<\/scp> in Imiquimod\u2010Induced Psoriasis Models of <scp>C57BL<\/scp>\/6 Mice"],"prefix":"10.1111","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4446-6227","authenticated-orcid":false,"given":"Jue","family":"Tang","sequence":"first","affiliation":[{"name":"Department of Dermatology, Beijing Chao\u2010Yang Hospital Capital Medical University  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siqi","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Beijing Ditan Hospital Capital Medical University  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9124-6230","authenticated-orcid":false,"given":"Yanqian","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Beijing Chao\u2010Yang Hospital Capital Medical University  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huijuan","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Capital Institute of Pediatrics Capital Medical University  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Beijing Chao\u2010Yang Hospital Capital Medical University  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Beijing Chao\u2010Yang Hospital Capital Medical University  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Renmin Hospital Hubei University of Medicine  Shiyan Hubei China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinping","family":"Jin","sequence":"additional","affiliation":[{"name":"Shanghai Institute of Immunology, Precision Research Center for Refractory Diseases, Shanghai General Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3706-9967","authenticated-orcid":false,"given":"Yanling","family":"He","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Beijing Chao\u2010Yang Hospital Capital Medical University  Beijing China"},{"name":"National Clinical Research Center for Skin and Immune Diseases Branch in Beijing Chaoyang Hospital  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,6,19]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0804595"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)61909-7"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2016.82"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)32549-6"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.14460"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2015.02.1127"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2023.10.018"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13555-024-01250-9"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.2147\/PRBM.S195181"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1186455"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20050500"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.03.021"},{"key":"e_1_2_10_14_1","first-page":"1665","article-title":"Efficacy and Safety of Ustekinumab, a Human Interleukin\u201012\/23 Monoclonal Antibody, in Patients With Psoriasis: 76\u2010Week Results From a Randomised, Double\u2010Blind, Placebo\u2010Controlled Trial (PHOENIX 1)","volume":"371","author":"Leonardi C. 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