{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T08:38:29Z","timestamp":1782895109826,"version":"3.54.5"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Chronic ultraviolet (UV) exposure superimposes inflammatory and matrix-degenerative insults on intrinsic aging to produce cutaneous photoaging, yet the cell-type-resolved circuits and druggable nodes driving this process remain poorly defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Chronic We established a chronic UVA+UVB-induced mouse model of photoaging and performed single-cell RNA sequencing of control, UV-exposed, and UV + ruxolitinib-treated dorsal skin to map photoaging and therapeutic response at cellular resolution.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Chronic Across 14 major lineages, UV exposure preserved overall cellular composition but induced a coordinated transcriptional network shift, marked by activation of JAK\u2013STAT\/IRF\/AP-1-driven inflammatory and oxidative-stress programs and suppression of developmental, DNA-repair, and differentiation modules. Fibroblast reclustering resolved eight states and identified a papillary-to-reticular transitional continuum with the highest transcriptional burden, integrating senescence-associated secretory phenotype and extracellular-matrix disassembly signatures and skewing pseudotime toward late, terminal states. Topical JAK1\/2 inhibition with ruxolitinib attenuated clinical and histological photoaging phenotypes, restored collagen and elastic fiber architecture, and rebalanced fibroblast trajectories by suppressing inflammatory\/stress pathways while reactivating basement-membrane, extracellular-matrix, adhesion, and wound-healing programs. Cross-lineage analysis further revealed reversal of conserved stress\u2013metabolic axes, including\n                      <jats:italic>Hmox1<\/jats:italic>\n                      ,\n                      <jats:italic>Gpx3<\/jats:italic>\n                      ,\n                      <jats:italic>Ucp2<\/jats:italic>\n                      , and\n                      <jats:italic>Nr4a2<\/jats:italic>\n                      , restoration of structural\u2013matrix programs involving Dcn, Gsn, and Nup210l, normalization of aging regulators such as\n                      <jats:italic>Cdkn1a<\/jats:italic>\n                      and\n                      <jats:italic>Trp53<\/jats:italic>\n                      , and re-establishment of dermal\u2013epidermal crosstalk through collagen IV\u2013syndecan and fibronectin\/laminin\u2013CD44\/\u03b1v\u03b21 signaling.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Chronic These findings identify transitional fibroblasts as central executors of UV-driven dermal remodeling and support JAK1\/2 inhibition as a network-level strategy to restore dermal\u2013epidermal homeostasis in photoaged skin.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1748123","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T07:16:49Z","timestamp":1782890209000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Single-cell atlas of photoaged skin reveals JAK-STAT blockade as a strategy to reverse dermal remodeling"],"prefix":"10.3389","volume":"17","author":[{"given":"Mingwang","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Dermatology, Southwest Hospital, Army Medical University","place":["Chongqing, 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University","place":["Xinxiang, Henan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Luo","sequence":"additional","affiliation":[{"name":"Biological Therapy Center, Seventh Medical Center of Chinese People\u2019s Liberation Army (PLA) General Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haima","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, No. 215 Hospital of Shaanxi Nuclear Industry","place":["Xianyang, Shaanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongya","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Seventh Medical Center of Chinese People\u2019s Liberation Army (PLA) General Hospital","place":["Beijing, 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