ORIGINAL RESEARCH article
Front. Immunol.
Sec. B Cell Biology
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1664199
This article is part of the Research TopicImmune Challenges and Innovations in Lipid-Encapsulated BiotherapeuticsView all 4 articles
Bexarotene signaling in human B and T lymphocytes induces gut homing receptor expression
Provisionally accepted
Sina Kaiser1*
Ina Suhrkamp1Jinru He2Charlotte Helf1
Christian David Sadik3Michael Weichenthal1
Guido Heine1- 1University Medical Center Schleswig-Holstein, Kiel, Germany
- 2Christian-Albrechts-Universitat zu Kiel, Kiel, Germany
- 3Universitat zu Lubeck, Lübeck, Germany
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Background: 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. Objective: To determine the impact of the RXR-ligand bexarotene (BXR) on the activation and differentiation of human B and T lymphocytes. Methods: In vitro BXR stimulation of human CD19+ B cells and CD4+ T helper cells was investigated regarding retinoid target gene expression by 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. Results: BXR induces the canonical retinoid target gene CD38 in B cells and T cells (6-fold and 3-fold, respectively). BXR increased CD38 surface protein expression on B cells 2-fold and plasmablast differentiation 3-fold. The frequency of the gut homing receptors CCR9 and integrin β7 was doubled on T and B cells after BXR stimulation, while 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 %). Conclusion: BXR via RXRs directly targets B and T lymphocytes inducing retinoid target gene expression including gut homing receptors.
Keywords: B cells, Bexarotene, Homing, Lymphocytes, Retinoid, Rexinoid, T cells
Received: 11 Jul 2025; Accepted: 16 Sep 2025.
Copyright: © 2025 Kaiser, Suhrkamp, He, Helf, Sadik, Weichenthal and Heine. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Sina Kaiser, skaiser@dermatology.uni-kiel.de
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