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Immunol."],"abstract":"<jats:p>Psoriasis is a chronic, relapsing, immune-mediated inflammatory dermatosis characterized by aberrant keratinocyte hyperproliferation and prominent infiltration of inflammatory leukocytes. Among the NF-\u03baB transcription factor family, c-Rel is the first member conclusively implicated as a psoriasis susceptibility gene, and its dysregulated expression positively correlates with clinical disease activity. Mechanistically, c-Rel orchestrates pathogenic inflammation by coordinating immune-cell differentiation programs and inflammatory cytokine production, while also contributing to keratinocyte proliferation and inflammatory responses in non-hematopoietic compartments. Emerging therapeutic approaches that modulate c-Rel, ranging from biologics and small-molecule inhibitors to nucleic-acid-based interventions, have shown encouraging efficacy in both clinical study and experimental psoriasis models. However, key translational hurdles remain, including suboptimal delivery, incomplete target-cell specificity, and long-term safety concerns. Deeper delineation of upstream activation cues and cell-type-restricted c-Rel regulatory circuits will be essential to enable precision targeting of c-Rel in psoriasis.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1849308","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T05:46:23Z","timestamp":1783403183000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["NF-\u03baB-c-Rel in psoriasis: genetic susceptibility, immunopathogenic circuits, and emerging therapeutic opportunities"],"prefix":"10.3389","volume":"17","author":[{"given":"Ruiling","family":"Liu","sequence":"first","affiliation":[{"name":"Joint National Laboratory for Antibody Drug Engineering, Henan University School of Medicine","place":["Kaifeng, China"]},{"name":"School of Basic Medical Sciences, Henan University School of Medine","place":["Kaifeng, 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