Invariant NKT cells modulate the suppressive activity of IL-10-secreting neutrophils differentiated with serum amyloid A.
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.
De Santo
Carmela
C
Medical Research Council Human Immunology Unit, Nuffield Department of Medicine, Medical Research Council Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
Arscott
Ramon
R
Booth
Sarah
S
Karydis
Ioannis
I
Jones
Margaret
M
Asher
Ruth
R
Salio
Mariolina
M
Middleton
Mark
M
Cerundolo
Vincenzo
V
D000818:Animals; D002454:Cell Differentiation / Q000276:immunology*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology*; D008545:Melanoma / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D055611:Natural Killer T-Cells / Q000276:immunology*; D009504:Neutrophils / Q000166:cytology / Q000276:immunology*; D000685:Serum Amyloid A Protein / Q000276:immunology*
D000685:Serum Amyloid A Protein; D016753:Interleukin-10