{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T05:46:06Z","timestamp":1785735966399,"version":"3.56.0"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T00:00:00Z","timestamp":1785715200000},"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:p>\n                    Fatty acid-binding proteins (FABPs) are intracellular lipid chaperones that regulate gene expression by controlling lipid trafficking within subcellular organelles. Among them, FABP4 is primarily expressed in adipocytes and macrophages and has been implicated in inflammatory responses in adipose tissue; however, its role in skin inflammation remains poorly understood. Here, we investigated the immunomodulatory role of FABP4 using human psoriatic skin samples, single-cell RNA sequencing, and an imiquimod-induced mouse model of psoriasis. We further employed pharmacologic inhibition and genetic modulation of FABP4 to assess its effects on macrophage polarization, along with transcription factor regulon analyses to identify downstream regulatory mechanisms. FABP4 was highly expressed in macrophages infiltrating psoriatic skin, and\n                    <jats:italic>in vivo<\/jats:italic>\n                    pharmacological inhibition of FABP4 attenuated psoriasiform skin inflammation and shifted macrophage phenotypes, suppressing M1-associated features while promoting CD206-expressing alternatively activated macrophages. For mechanistic insights, we examined the regulon activity of transcription factors associated with macrophage polarization in psoriatic skin and identified an association between PPARG and macrophage polarization; our\n                    <jats:italic>in vivo<\/jats:italic>\n                    and\n                    <jats:italic>in vitro<\/jats:italic>\n                    experiments further demonstrated that FABP4 inhibition restored PPARG expression and activity in psoriasis mice, which was decreased by imiquimod application. Overall, our study demonstrated that FABP4 plays a critical role in skin inflammation by modulating macrophage polarization through PPARG regulation, suggesting that targeting FABP4 may represent a potential therapeutic strategy for psoriasis and other inflammatory skin diseases.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1830077","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T05:31:03Z","timestamp":1785735063000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Inhibition of fatty acid-binding protein 4 alleviates psoriasis-like skin inflammation by modulating macrophage polarization"],"prefix":"10.3389","volume":"17","author":[{"given":"Bo Mi","family":"Kang","sequence":"first","affiliation":[{"name":"Department of Dermatology, Seoul National University College of Medicine","place":["Seoul, Republic of Korea"]},{"name":"Department of Dermatology, Seoul National 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Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine Suh-Yun","family":"Joh","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Seoul National University Graduate School","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyo Jeong","family":"Nam","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Seoul National University Graduate School","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soyoung","family":"Jeong","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Seoul National University Graduate School","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun Woo","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Seoul National University Graduate School","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeong Eun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Hanyang University College of Medicine","place":["Seoul, Republic of Korea"]},{"name":"Hanyang Institute of Bioscience and Biotechnology, Hanyang University","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae-Gyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Severance Hospital, Cutaneous Biology Research Institute, Yonsei University College of Medicine","place":["Seoul, Republic of Korea"]},{"name":"Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun Je","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Seoul National University Graduate School","place":["Seoul, Republic of Korea"]},{"name":"Cancer Research Institute, Seoul National University College of Medicine","place":["Seoul, Republic of Korea"]},{"name":"Interdisciplinary Program in Artificial Intelligence (IPAI), Seoul National University","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chong Won","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Seoul National University College of Medicine","place":["Seoul, Republic of Korea"]},{"name":"Department of Dermatology, Seoul National University Bundang Hospital","place":["Seongnam, Republic of Korea"]},{"name":"Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center","place":["Seoul, Republic of 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