<p>We investigated how selective inhibition of galectin-1 and galectin-3 expressed by COLO 201 colorectal adenocarcinoma cells modulates CD4+ T lymphocyte differentiation <i>in vitro</i>. The mRNA expression levels of the transcription factors T-bet (<i>TBX21</i>), RORC2, and Foxp3 were analyzed in peripheral blood mononuclear cells (PBMCs) from colorectal cancer patients and healthy donors following co-culture with COLO 201 cells in the presence of galectin-1 inhibitor OTX 008, galectin-3 inhibitor GB1107, or both. Inhibition of galectin-1 in co-cultures increased <i>TBX21</i> and <i>RORC2</i> mRNA expression while suppressing <i>FOXP3</i> in PBMCs from both groups. In patient-derived PBMCs, galectin-3 inhibition produced a similar effect. Conversely, in healthy donor cells, galectin-3 blockade suppressed <i>RORC2</i> and induced <i>FOXP3</i> expression. Notably, the most pronounced downregulation of <i>FOXP3</i> was achieved by simultaneously inhibiting both galectins.</p>

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Colon Adenocarcinoma Cell-Derived Galectins-1,3 Modulate Differentiation of CD4+ T Lymphocytes In Vitro

  • V. S. Poletika,
  • G. V. Reingardt,
  • A. V. Kurnosenko,
  • Yu. V. Kolobovnikova,
  • O. I. Urazova

摘要

We investigated how selective inhibition of galectin-1 and galectin-3 expressed by COLO 201 colorectal adenocarcinoma cells modulates CD4+ T lymphocyte differentiation in vitro. The mRNA expression levels of the transcription factors T-bet (TBX21), RORC2, and Foxp3 were analyzed in peripheral blood mononuclear cells (PBMCs) from colorectal cancer patients and healthy donors following co-culture with COLO 201 cells in the presence of galectin-1 inhibitor OTX 008, galectin-3 inhibitor GB1107, or both. Inhibition of galectin-1 in co-cultures increased TBX21 and RORC2 mRNA expression while suppressing FOXP3 in PBMCs from both groups. In patient-derived PBMCs, galectin-3 inhibition produced a similar effect. Conversely, in healthy donor cells, galectin-3 blockade suppressed RORC2 and induced FOXP3 expression. Notably, the most pronounced downregulation of FOXP3 was achieved by simultaneously inhibiting both galectins.