{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T18:58:18Z","timestamp":1790708298052,"version":"4.1.0"},"reference-count":30,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunity Inflam &amp;amp; Disease"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Macrophage\u2013keratinocyte crosstalk is an important component of cutaneous inflammatory responses. Psoriasis is a chronic inflammatory skin disease characterized by dysregulated keratinocyte proliferation and immune dysfunction. While macrophage pro\u2010inflammatory activation is known to exacerbate psoriatic inflammation, the underlying molecular mechanisms remain incompletely understood. TRIM28, a multifunctional regulatory protein, may play a role in this process, but whether TRIM28 regulates macrophage\u2013keratinocyte crosstalk in a psoriasis\u2010relevant inflammatory context remains unclear. The present study was designed as an in vitro mechanistic investigation and does not establish TRIM28 dysregulation in human psoriasis. Therefore, psoriasis is discussed only as a potential disease context, rather than as a conclusion directly supported by the present data.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Human THP\u20101 monocytes were differentiated into macrophages and subjected to TRIM28 knockdown or overexpression. Macrophage polarization status was evaluated using a limited panel of conventional M1\u2010like\/M2\u2010like\u2010associated markers via flow cytometry (CD68\/CD86\/CD206), cytokine secretion (ELISA for IL\u20106, TNF\u2010\u03b1, IL\u201010), and marker expression (iNOS\/Arg1 by Western blot). The NLRP3\/SGT1 axis and NLRP3 SUMOylation were evaluated using Western blot and co\u2010immunoprecipitation, respectively. Inflammasome\u2010associated activation was further assessed by detecting cleaved caspase\u20101 and mature IL\u20101\u03b2 expression using Western blot and secreted IL\u20101\u03b2 using ELISA. The interaction between TRIM28 and NLRP3 was examined by co\u2010immunoprecipitation. Functional impacts on keratinocytes were examined using a Transwell co\u2010culture system with HaCaT cells, measuring proliferation (CCK\u20108) and invasion (Transwell assays). Rescue experiments involved NLRP3\/SGT1 knockdown or SUMOylation inhibition (2\u2010D08).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>TRIM28 overexpression promoted macrophage M1\u2010like\/pro\u2010inflammatory marker expression, increased pro\u2010inflammatory cytokine secretion, and elevated NLRP3 and SGT1 expression, while enhancing NLRP3 SUMOylation. TRIM28 overexpression also increased cleaved caspase\u20101, mature IL\u20101\u03b2, and IL\u20101\u03b2 secretion, whereas TRIM28 knockdown exerted the opposite effects. Co\u2010immunoprecipitation further showed an interaction between TRIM28 and NLRP3. Conversely, TRIM28 knockdown induced a shift toward an M2\u2010like\/anti\u2010inflammatory marker profile and reduced inflammation. In co\u2010culture, TRIM28\u2010overexpressing macrophages significantly enhanced HaCaT cell proliferation and invasion. These effects were reversed by NLRP3\/SGT1 silencing or SUMOylation inhibition, supporting the involvement of the NLRP3\/SGT1 axis and NLRP3 SUMOylation in TRIM28\u2010mediated actions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>TRIM28 promotes macrophage pro\u2010inflammatory polarization\u2010like changes by activating the NLRP3\/SGT1 axis via NLRP3 SUMOylation, subsequently promoting keratinocyte proliferation and invasion in an in vitro macrophage\u2013keratinocyte co\u2010culture system. These findings suggest a potential mechanism relevant to inflammatory macrophage\u2013keratinocyte interactions, but validation in psoriatic tissues, animal models, and clinical datasets is required before TRIM28 can be implicated in psoriasis pathogenesis. Accordingly, the present study should be interpreted as a basic mechanistic investigation rather than clinical or disease\u2010level evidence linking TRIM28 to psoriasis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/iid3.70522","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T12:57:01Z","timestamp":1789045021000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["TRIM28 Promotes Keratinocyte Proliferation and Invasion by Activating NLRP3\/SGT1 Axis\u2010Mediated Macrophage Pro\u2010Inflammatory Polarization in an In Vitro Macrophage\u2013Keratinocyte Co\u2010Culture Model"],"prefix":"10.1002","volume":"14","author":[{"given":"Zhe","family":"Gao","sequence":"first","affiliation":[{"name":"Department of Dermatology Hangzhou Third People's Hospital Hangzhou Zhejiang 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