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Myeloid suppressor cells require membrane TNFR2 expression for suppressive activity

Johannes Polz1, Annika Remke1, Sabine Weber1

  • 1Institute of Immunology, University of Regensburg Regensburg, Germany.

Immunity, Inflammation and Disease
|November 18, 2014
PubMed

Insights

Tumor Necrosis Factor Receptor 2 (TNFR2) is crucial for generating myeloid-derived suppressor cells (MDSC). Membrane-bound TNFR2 expression dictates the generation and function of these suppressive monocytic cells.

Area of Science:

  • Immunology
  • Cell Biology

Background:

  • Tumor Necrosis Factor (TNF) and its receptor TNFR2 play roles in myeloid-derived suppressor cell (MDSC) generation.
  • Understanding the precise mechanism of TNFR2's influence on MDSC is essential.

Purpose of the Study:

  • To investigate the role of TNFR2 in mediating TNF's effects on myeloid cells.
  • To determine if TNFR2 signaling is required for the development and function of monocytic MDSC.

Main Methods:

  • Comparison of myeloid cells from TNFR2-deficient mice and wild-type mice.
  • Co-culture experiments of bone marrow cells from both mouse lines.
  • Adoptive transfer of TNFR2-deficient bone marrow cells into wild-type hosts.

Main Results:

  • TNFR2-deficient myeloid cells exhibited reduced production of nitric oxide (NO) and IL-6.
  • Immature monocytic MDSC (CD11b(+) CD11c(-) Ly6C(+) Ly6G(-)) were primarily affected.
  • TNFR2-deficient MDSC showed decreased suppressive activity on T cell proliferation.
  • Functional deficits were dependent on membrane-bound TNFR2 expression, not soluble factors.

Conclusions:

  • Membrane-bound TNFR2 expression is critical for the generation and functional capacity of monocytic MDSC.
  • TNFR2 signaling directly impacts MDSC development and suppressive functions.
Keywords:
Immune suppressioninflammationtumor necrosis factor

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