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.
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Acknowledgements
We thank L. Van Kaer (Vanderbilt University School of Medicine) for Cd1d−/− (CD45.2+/+) mice; R. Lisle and K. Hollowood for help in preparing melanoma sample sections and analyzing stained samples; G. Napolitani, A. Stock and M. Johnson for discussions and critical reading of the manuscript; and P. Polzella for technical support. Supported by Cancer Research UK (C399/A2291), the UK Medical Research Council, The Wellcome Trust (084923/Z/08/Z), the Cancer Research Institute, the Ludwig Institute for Cancer Research (V.C.), the Oxford National Institute for Health Research Biomedical Research Centre (M.M., R. Asher and M.J.) and the Oxford Experimental Cancer Medicine Centre (for clinical sample processing).
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C.D.S. designed and did the experiments, prepared the figures and contributed to the writing of the manuscript; R. Arscott did specific experiments; I.K. and M.M. obtained consent from patients with melanoma and collected blood samples; S.B., M.J. and R. Asher did tissue staining of melanoma sections; M.S. provided reagents and contributed to the writing of the manuscript; and V.C. designed the experiments and wrote the manuscript.
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De Santo, C., Arscott, R., Booth, S. et al. Invariant NKT cells modulate the suppressive activity of IL-10-secreting neutrophils differentiated with serum amyloid A. Nat Immunol 11, 1039–1046 (2010). https://doi.org/10.1038/ni.1942
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DOI: https://doi.org/10.1038/ni.1942
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