Invariant NKT Cells Modulate the Suppressive Activity of IL-10-secreting Neutrophils Differentiated With Serum Amyloid A

Nat Immunol. 2010 Nov;11(11):1039-46. doi: 10.1038/ni.1942. Epub 2010 Oct 3.

Abstract

Neutrophils are the main effector cells during inflammation, but they can also control excessive inflammatory responses by secreting anti-inflammatory cytokines. However, the mechanisms that modulate their plasticity remain unclear. We now show that systemic serum amyloid A 1 (SAA-1) controls the plasticity of neutrophil differentiation. SAA-1 not only induced anti-inflammatory interleukin 10 (IL-10)-secreting neutrophils but also promoted the interaction of invariant natural killer T cells (iNKT cells) with those neutrophils, a process that limited their suppressive activity by diminishing the production of IL-10 and enhancing the production of IL-12. Because SAA-1-producing melanomas promoted differentiation of IL-10-secreting neutrophils, harnessing iNKT cells could be useful therapeutically by decreasing the frequency of immunosuppressive neutrophils and restoring tumor-specific immune responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / immunology*
  • Cell Line, Tumor
  • Female
  • Humans
  • Interleukin-10 / immunology*
  • Melanoma / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Natural Killer T-Cells / immunology*
  • Neutrophils / cytology
  • Neutrophils / immunology*
  • Serum Amyloid A Protein / immunology*

Substances

  • Serum Amyloid A Protein
  • Interleukin-10