{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T06:03:36Z","timestamp":1784527416511,"version":"3.55.0"},"reference-count":92,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2023YFC2508102"],"award-info":[{"award-number":["2023YFC2508102"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["824B200225, 82373879"],"award-info":[{"award-number":["824B200225, 82373879"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003392","name":"Natural Science Foundation of Fujian Province","doi-asserted-by":"publisher","award":["2024J011009"],"award-info":[{"award-number":["2024J011009"]}],"id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012172","name":"Double First Class University Plan","doi-asserted-by":"publisher","award":["DFC2024004"],"award-info":[{"award-number":["DFC2024004"]}],"id":[{"id":"10.13039\/501100012172","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>Allergic contact dermatitis (ACD) and atopic dermatitis (AD) are driven by distinct T cell programs, and safe long-term topical therapies remain limited. Dermal fibroblasts (dFBs) have emerged as active immunomodulators, but whether they can be therapeutically targeted remains unexplored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Here we developed MDI1228, a novel topical pan\u2011JAK inhibitor with nanomolar potency against JAK1\/2\/3\/TYK2 (IC\u2085\u2080 0.11-0.85 nM) and high selectivity. MDI1228 was evaluated in DNFB\u2011induced ACD and MC903\u2011induced AD mouse models, as well as in primary mouse and human cell\u2011based assays.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Topical MDI1228 ameliorated both ACD and AD in mice, reducing T cell infiltration and cytokine production. Mechanistically, MDI1228 not only directly inhibited T cell activation and cytokine production but also disrupted fibroblast\u2011T cell crosstalk by reducing dFB\u2011derived chemokine expression. Single\u2011cell transcriptomics identified dFBs as the primary source of CXCL9\/10 in ACD and CCL2 in AD. Conditioned medium and neutralization experiments demonstrated that CXCL9\/10\u2011CXCR3 and CCL2\u2011CCR2 signaling axes contribute to T cell polarization in a context\u2011dependent manner. Compared with glucocorticoids, prolonged topical application of MDI1228 showed minimal systemic toxicity and preserved tissue homeostasis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings identify dFBs as a central therapeutic node and demonstrate that MDI1228, by directly targeting T cells and disrupting dFB\u2011derived chemokine axes via JAK inhibition, offers a potent and safe topical treatment for both ACD and AD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1875876","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T05:34:38Z","timestamp":1784525678000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["MDI1228, a topical pan-JAK inhibitor, disrupts dermal fibroblast-T cell chemokine crosstalk to resolve allergic contact and atopic dermatitis"],"prefix":"10.3389","volume":"17","author":[{"given":"Youxi","family":"Liu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Cellular Stress Biology, School of Pharmaceutical Sciences, Xiamen University","place":["Xiamen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meimei","family":"Yin","sequence":"additional","affiliation":[{"name":"Dermatology Hospital of Jiangxi Province, Jiangxi Provincial Clinical Research Center for Skin Diseases, Candidate Branch of National Clinical Research Center for Skin Diseases, JXHC Key Laboratory of Skin Infection and Immunity, The Affiliated Dermatology Hospital of Nanchang University","place":["Nanchang, Jiangxi, China"]},{"name":"State Key Laboratory of Cellular Stress Biology, School of Pharmaceutical Sciences, Xiamen University","place":["Xiamen, 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