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Cited by 55Phagocytosis and Immune RegulationInflammation biomarkers and pathwaysNeutrophil, Myeloperoxidase and Oxidative Mechanisms

Inflammation-induced proteolytic processing of the SIRPα cytoplasmic ITIM in neutrophils propagates a proinflammatory state

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Zen, Ke, Guo, Yalan, Bian, Zhen, Lv, Zhiyuan, Zhu, Dihan, Ohnishi, Hiroshi, Matozaki, Takashi, Liu, Yuan·2013·Nature Communications
DOI 10.1038/ncomms3436PMC PMC5875419
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Abstract

Signal regulatory protein α (SIRPα), an immunoreceptor tyrosine-based inhibitory motif (ITIM)-containing receptor, is an essential negative regulator of leukocyte inflammatory responses. Here we report that SIRPα cytoplasmic signalling ITIMs in neutrophils are cleaved during active inflammation and that the loss of SIRPα ITIMs enhances the polymorphonuclear leukocyte (PMN) inflammatory response. Using human leukocytes and two inflammatory models in mice, we show that the cleavage of SIRPα ITIMs in PMNs but not monocytes occurs at the post-acute stage of inflammation and correlates with increased PMN recruitment to inflammatory loci. Enhanced transmigration of PMNs and PMN-associated tissue damage are confirmed in mutant mice expressing SIRPα but lacking the ITIMs. Moreover, the loss of SIRPα ITIMs in PMNs during colitis is blocked by an anti-interleukin-17 (IL-17) antibody. These results demonstrate a SIRPα-based mechanism that dynamically regulates PMN inflammatory responses by generating a CD47-binding but non-signalling SIRPα 'decoy'.

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Cited by

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Authors
Zen, K., Guo, Y., Bian, Z., Lv, Z., Zhu, D., Ohnishi, H., Matozaki, T., & Liu, Y.
Affiliations
  • State Key Laboratory of Pharmaceutical Biotechnology (CN)
  • Georgia State University (US)
  • Gunma University (JP)
Corresponding author
Liu, Yuan
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2013-09-12
Volume
4
Issue
1
Pages
2436-2436
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/ncomms3436
PMC
PMC5875419
OpenAlex
W1992108947
Cited by
55
References
0
Citations by year
2026: 4 · 2025: 5 · 2024: 8 · 2023: 4 · 2022: 3 · 2021: 5 · 2020: 7 · 2019: 1 · 2018: 1 · 2017: 3 · 2016: 7 · 2015: 4 · 2014: 3
FWCI
2.58
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
Funders
  • American Cancer Society
  • National Natural Science Foundation of China (30988003)
  • National Institutes of Health
  • Japan Society for the Promotion of Science (23370061, 23500437)
  • National Key Research and Development Program of China (2012CB517603)
  • National Institute of Allergy and Infectious Diseases (R01AI106839)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK 62894, K01DK062894)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
  • Life Sciences › Immunology and Microbiology › Immunology › Inflammation biomarkers and pathways
  • Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
Keywords
SIRPα, ITIM, neutrophils, proteolytic processing, inflammation, CD47, decoy receptor, negative regulation of inflammation, neutrophil transmigration, neutrophil recruitment, colitis, IL-17
MeSH terms
Animals, Antigens, Differentiation, Cell Movement, Cell Separation, Cytoplasm, Disease Models, Animal, Female, Flow Cytometry, Humans, Inflammation, Mice, Inbred C57BL, Neutrophils, Protein Binding, Receptors, Immunologic, Blotting, Western, Gene Deletion, Sequence Deletion, Amino Acid Motifs, Mice, CD47 Antigen, Serine Proteases, Proteolysis

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