Bexarotene signaling in human B and T lymphocytes induces gut-homing receptor expression

Sina Kaiser1, Ina Suhrkamp1, Jinru He2

  • 1Department of Dermatology, Venereology, and Allergy, University Hospital Schleswig-Holstein, Kiel, Germany.

Frontiers in Immunology
|October 24, 2025
PubMed
Abstract

Insights

Bexarotene (BXR) activates retinoid X receptors (RXRs) in human B and T lymphocytes. This immune cell modulation impacts gut-homing receptors and CD38 expression, influencing immune responses.

Area of Science:

  • Immunology
  • Molecular Biology
  • Pharmacology

Background:

  • Retinoic acid receptors (RARs) influence human lymphocyte function, affecting humoral and intestinal immunity.
  • The role of retinoid X receptors (RXRs) in these processes remains unclear.

Purpose of the Study:

  • To investigate the effect of the RXR ligand bexarotene (BXR) on human B and T lymphocyte activation and differentiation.
  • To elucidate the molecular mechanisms underlying BXR's impact on lymphocyte populations.

Main Methods:

  • In vitro studies using human CD19+ B cells and CD4+ T helper cells stimulated with BXR.
  • Quantitative PCR (qPCR) and flow cytometry to assess retinoid target gene expression and protein levels.
  • Validation in peripheral blood lymphocytes from cutaneous T-cell lymphoma (CTCL) patients undergoing BXR treatment.

Main Results:

  • BXR significantly upregulated the retinoid target gene CD38 in both B and T cells.
  • BXR increased CD38 surface protein expression and promoted plasmablast differentiation in B cells.
  • BXR stimulation enhanced gut-homing receptors (CCR9, integrin β7) on lymphocytes while decreasing cutaneous lymphocyte-associated antigen (CLA) on B cells.
  • In CTCL patients, BXR treatment correlated with reduced frequencies of gut-homing receptors on memory T and B cells.

Conclusions:

  • Bexarotene (BXR), acting through retinoid X receptors (RXRs), directly modulates human B and T lymphocytes.
  • BXR induces retinoid target gene expression, including key gut-homing receptors, thereby influencing lymphocyte trafficking and immune responses.