{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T06:11:03Z","timestamp":1759903863660,"version":"build-2065373602"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T00:00:00Z","timestamp":1759881600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Retinoic acid (RA) receptors (RARs) in human lymphocytes modulate the humoral and intestinal immune response by regulating target genes, including CD38, TGM2, and gut-homing markers. The impact of retinoid X receptors (RXRs) on this process is elusive.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To determine the impact of the RXR ligand bexarotene (BXR) on the activation and differentiation of human B and T lymphocytes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p><jats:italic>In vitro<\/jats:italic> BXR stimulation of human CD19<jats:sup>+<\/jats:sup> B cells and CD4<jats:sup>+<\/jats:sup> T helper cells was investigated regarding retinoid target gene expression using qPCR and flow cytometry and validated in peripheral B and T lymphocytes of patients with cutaneous T-cell lymphoma (CTCL) with and without BXR treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>BXR induced the canonical retinoid target gene <jats:italic>CD38<\/jats:italic> in B cells and T cells (sixfold and threefold, respectively). BXR increased CD38 surface protein expression on B cells twofold and plasmablast differentiation threefold. The frequency of the gut-homing receptors CCR9 and integrin \u03b27 was doubled on T and B cells after BXR stimulation, while cutaneous leucocyte-associated antigen (CLA) expression was decreased in B cells. Under BXR treatment, a reduced frequency of cells with these gut-homing receptors was observed in the blood of CTCL patients regarding memory T cells (mean off: 1.9%; on: 0.6%) and B cells (mean off: 5.7%, on: 4%).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>BXR via RXRs directly targets B and T lymphocytes, inducing retinoid target gene expression, including gut-homing receptors.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1664199","type":"journal-article","created":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T05:40:28Z","timestamp":1759902028000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Bexarotene signaling in human B and T lymphocytes induces gut-homing receptor 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