{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T05:47:26Z","timestamp":1785822446779,"version":"3.56.0"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"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. Cell Dev. Biol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Psoriasis is a chronic immune-mediated inflammatory skin disorder hallmarked by keratinocyte hyperproliferation and impaired apoptosis. N6-methyladenosine (m6A) RNA modification is emerging as a critical regulator of inflammatory gene expression. RNA-binding motif protein 15 (RBM15), a core m6A methyltransferase complex adaptor, promotes oncogenic processes across tissue types; however, its role in psoriatic keratinocyte biology and its potential regulation of interleukin-10 (IL-10)\u2014a pivotal anti-apoptotic and immunomodulatory cytokine\u2014remain unexplored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Single-cell RNA sequencing data from a publicly deposited psoriasis dataset (GSE248121; 23,851 cells from two paired libraries) were analyzed using Seurat, Monocle3, CellChat, and pySCENIC. Bulk transcriptomic datasets (GSE54456, GSE30999) were used for cross-dataset validation of RBM15 and IL10 expression.\n                      <jats:italic>In vitro<\/jats:italic>\n                      , RBM15 was silenced in IL-17A\/M5-stimulated HaCaT keratinocytes by siRNA. m6A modification of IL10 mRNA was mapped by methylated RNA immunoprecipitation-qPCR (MeRIP-qPCR) and validated by mRNA stability assay, luciferase reporter, and YTHDF2 RNA immunoprecipitation. Apoptosis was quantified by flow cytometry (Annexin V\/PI), caspase-3\/7 activity, CCK-8 viability, and Western blotting of Bcl-2 family proteins and JAK1\/STAT3 pathway components.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Integrated single-cell analysis resolved 23,851 cells into six principal cell types across psoriatic lesional (PP) and clinically normal (NS) skin. RBM15 was markedly upregulated in psoriatic keratinocytes (log2FC = 1.93 [fold change \u22483.82] \u00b1 0.31 vs. NS; p &amp;lt; 0.001) and correlated inversely with IL10 along keratinocyte pseudotime trajectories (r = \u22120.52, p &amp;lt; 0.001). Cross-dataset validation confirmed concordant RBM15 upregulation and IL10 downregulation in PP lesions. Mechanistically, RBM15 installed m6A marks at two RRACH motifs in the IL10 3\u2032UTR, promoting YTHDF2-mediated mRNA degradation (half-life reduction 53.3%; p &amp;lt; 0.001) and 62% suppression of IL10 protein.\n                      <jats:italic>In vitro<\/jats:italic>\n                      , RBM15 knockdown restored IL10, reduced apoptosis from 22.8% to 8.4% (p &amp;lt; 0.001), augmented JAK1\/STAT3 phosphorylation, and elevated Bcl-2\/Bcl-xL while suppressing Bax and cleaved caspase-3. IL10 neutralization fully reversed these pro-survival effects.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      RBM15-driven m6A modification of IL10 mRNA constitutes a previously unrecognized epitranscriptomic mechanism suppressing IL-10-mediated survival signaling in psoriatic keratinocytes. Targeting the RBM15\u2013m6A\u2013IL10 axis represents a mechanistically grounded and potentially tractable therapeutic direction for psoriasis, pending further\n                      <jats:italic>in vivo<\/jats:italic>\n                      and clinical validation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcell.2026.1897812","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T05:38:28Z","timestamp":1785821908000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrative single-cell transcriptomic and epitranscriptomic analysis of the RBM15\u2013m6A\u2013IL10 regulatory axis in psoriatic keratinocytes"],"prefix":"10.3389","volume":"14","author":[{"given":"Mo","family":"Li","sequence":"first","affiliation":[{"name":"Department of Dermatology, The First Affiliated Hospital of Qiqihar Medical University","place":["Qiqihar, Heilongjiang Province, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuyao","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The First Affiliated Hospital of Qiqihar Medical University","place":["Qiqihar, Heilongjiang Province, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengcheng","family":"Zhu","sequence":"additional","affiliation":[{"name":"Academic Affairs Office, The First Affiliated Hospital of Qiqihar Medical University","place":["Qiqihar, Heilongjiang Province, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Publicity, The Second Affiliated Hospital of Qiqihar Medical University","place":["Qiqihar, Heilongjiang Province, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Second Affiliated Hospital of Qiqihar Medical University","place":["Qiqihar, Heilongjiang Province, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1124\/pr.55.2.4","article-title":"Interleukin-10 Therapy\u2014Review of a new approach","volume":"55","author":"Asadullah","year":"2003","journal-title":"Pharmacol. 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