title: Invariant NKT cells modulate the suppressive activity of IL-10-secreting neutrophils differentiated with serum amyloid A.
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.
authors.affiliation: Medical Research Council Human Immunology Unit, Nuffield Department of Medicine, Medical Research Council Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
authors.forename: Carmela
authors.initials: C
authors.lastname: De Santo
authors.forename: Ramon
authors.initials: R
authors.lastname: Arscott
authors.forename: Sarah
authors.initials: S
authors.lastname: Booth
authors.forename: Ioannis
authors.initials: I
authors.lastname: Karydis
authors.forename: Margaret
authors.initials: M
authors.lastname: Jones
authors.forename: Ruth
authors.initials: R
authors.lastname: Asher
authors.forename: Mariolina
authors.initials: M
authors.lastname: Salio
authors.forename: Mark
authors.initials: M
authors.lastname: Middleton
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Cerundolo
mesh_terms: 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*
chemical_list: D000685:Serum Amyloid A Protein; D016753:Interleukin-10