{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:54:41Z","timestamp":1790747681399,"version":"4.1.0"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Psoriasis is a chronic inflammatory skin disease characterized by aberrant keratinocyte proliferation and dysregulated immune responses. Increasing evidence suggests that reciprocal communication between tissue-resident keratinocytes and infiltrating immune cells shapes the inflammatory microenvironment and governs disease progression. However, the molecular mechanisms underlying this immune-parenchymal crosstalk remain incompletely understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Here, we generate epidermal-specific Med1 conditional knockout (cKO) mice using the Cre-loxP system and induce psoriasis model with imiquimod (IMQ). To characterize immune-parenchymal interactions, single-cell RNA sequencing (scRNA-seq) was performed on lesional skin from cKO and wild-type (WT) mice. The underlying mechanisms governing keratinocyte-neutrophil communication were further investigated using flow cytometry, CellChat analysis, dual-luciferase reporter assays, transwell migration assays, and qRT-PCR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Epidermal deficiency of Med1 markedly alleviated IMQ-induced psoriasis, as evidenced by reduced epidermal thickness and diminished inflammatory cytokine production. The scRNA-seq result showed epithelial cells were reduced, accompanied with the significantly diminished neutrophil accumulation in cKO mice. Flow cytometry analysis also showed that CD45\n                      <jats:sup>+<\/jats:sup>\n                      Ly6G\n                      <jats:sup>+<\/jats:sup>\n                      neutrophils were found to be the most pronounced decreased relative to the other immune cells in cKO mice after IMQ. To further explore the dynamic changes of neutrophils in psoriasis, three novel neutrophil subtypes were identified, among which Cluster Nb exhibited a prominent chemotactic phenotype and was substantially diminished in cKO mice. Cell-cell communication analysis further identified the keratinocyte-derived CXCL-CXCR2 ligand-receptor axis as a key mediator of neutrophil recruitment. Mechanistically, keratinocyte-derived Med1 transcriptionally bound to CXCL1\/2\/3, thereby promoting CXCR2-dependent neutrophil chemotaxis during psoriasis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Collectively, our findings identify previously unrecognized neutrophil subtypes and demonstrates that epithelial Med1 regulates neutrophil phenotypes through the keratinocyte-derived CXCL-CXCR2 ligand-receptor axis. These findings uncover a microenvironmental mechanism governing neutrophil reprogramming and provide new insights into immune-parenchymal ligand-receptor communication in psoriasis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1935554","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:56:20Z","timestamp":1790744180000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Keratinocyte-derived CXCL-CXCR2 ligand-receptor axis by MED1 orchestrates neutrophil phenotypes during psoriasis"],"prefix":"10.3389","volume":"17","author":[{"given":"Yingxi","family":"Li","sequence":"first","affiliation":[{"name":"Health Science Center, Ningbo University","place":["Ningbo, Zhejiang, China"]},{"name":"Immunology Department, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Medical University","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junkai","family":"Huang","sequence":"additional","affiliation":[{"name":"Immunology Department, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Medical University","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guixin","family":"Wang","sequence":"additional","affiliation":[{"name":"Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Luo","sequence":"additional","affiliation":[{"name":"Immunology Department, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Medical University","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhikai","family":"Cao","sequence":"additional","affiliation":[{"name":"Health Science Center, Ningbo University","place":["Ningbo, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Guo","sequence":"additional","affiliation":[{"name":"Immunology Department, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Medical University","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianshu","family":"Yuan","sequence":"additional","affiliation":[{"name":"Immunology Department, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Medical University","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingwei","family":"Li","sequence":"additional","affiliation":[{"name":"Immunology Department, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Medical University","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Immunology Department, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Medical University","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weibin","family":"Xing","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Second Hospital of Tianjin Medical University","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lizhi","family":"Hu","sequence":"additional","affiliation":[{"name":"Immunology Department, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Medical University","place":["Tianjin, China"]},{"name":"Department of Ophthalmology, Second Hospital of Tianjin Medical University","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.4006","article-title":"Pathophysiology, clinical presentation, and treatment of psoriasis: A review","volume":"323","author":"Armstrong","year":"2020","journal-title":"Jama"},{"key":"B2","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1186\/s12967-023-03923-z","article-title":"Identification of 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