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Ligand-Regulated Expression of TNF Receptors 1 and 2 Determines Receptor-Mediated Functional Responses

Alina Alshevskaya1, Olga Koneva1, Irina Belomestnova1

  • 1Federal State Budgetary Scientific Institution "Research Institute of Fundamental and Clinical Immunology" (RIFCI), Novosibirsk, Russian Federation.

International Archives of Allergy and Immunology
|June 1, 2021
PubMed
Abstract

Insights

The expression density of tumor necrosis factor receptors (TNFR1/2) influences cell fate. High co-expression of TNFR1 and TNFR2 is critical for determining whether cells undergo apoptosis or proliferation.

Area of Science:

  • Immunology
  • Cell Biology
  • Cancer Research

Background:

  • The role of cytokine receptor expression levels in modulating biological effects is not fully understood.
  • Tumor necrosis factor (TNF) signaling through its receptors (TNFR1/2) plays a complex role in cell fate decisions.

Purpose of the Study:

  • To investigate the dose-dependent effects of TNF on the balance between proapoptotic and proliferation responses.
  • To determine how TNFR1 and TNFR2 expression density influences these cellular outcomes.

Main Methods:

  • Flow cytometry was used to characterize TNFR1/2 co-expression in various tumor cell lines.
  • The dose-dependent effects of recombinant human TNF (rhTNF) on cell cycle and apoptosis were analyzed.
  • Correlation and regression analyses were employed to assess associations between receptor expression and cellular responses.

Main Results:

  • In ZR-75/1 cells with high TNFR1/2 expression, increased receptor density reduced proliferation.
  • MOLT-4 cells with lower expression showed increased proliferation correlated with TNFR1+/TNFR2+ cell percentages.
  • K-562 and MCF-7 cell lines exhibited opposing effects despite similar expression profiles, while K-562 and ZR-75/1 showed similar effects with high double-positive cells.

Conclusions:

  • High TNFR1 expression does not invariably lead to apoptosis.
  • Simultaneous high expression of both TNFR1 and TNFR2 necessitates a critical proportion of double-positive cells to dictate either proapoptotic or proliferation pathways.
Keywords:
Cellular immunologyCytokine receptor expressionImmune regulationTNF-alpha

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