1. Immunoreceptors on neutrophils
- Author
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Hanke L. Matlung, Katka Szilagyi, Taco W. Kuijpers, Timo K. van den Berg, Dieke J van Rees, Amsterdam institute for Infection and Immunity, Molecular cell biology and Immunology, AII - Cancer immunology, and CCA - Cancer immunology
- Subjects
0301 basic medicine ,Syk, spleen tyrosine kinase ,Neutrophils ,Syk ,GBS, group B Streptococci ,MPO, myeloperoxidase ,RA, rheumatoid arthritis ,Plasma protein binding ,IVIg, intravenous immunoglobulins ,GPI, glycophosphatidylinositol ,Neutrophil Activation ,SLE, systemic lupus erythematosus ,PTPN6, tyrosine-protein phosphatase non-receptor type 6 ,0302 clinical medicine ,SLP-76, SH2 domain containing leukocyte protein of 76 kDa ,ERK, extracellular signal-regulated kinase ,PIP2, phosphatidylinositol (4,5)-bisphosphate ,ITAM ,SHP ,Immunology and Allergy ,Receptors, Immunologic ,SHP, SH2-domain containing phosphatase ,SOCS, suppressor of cytokine signaling proteins ,Antibody-dependent cell-mediated cytotoxicity ,SHIP, SH2-domain containing inositol phosphatase ,Effector ,DAP12, DNAX activation protein of 12 kDa ,hemic and immune systems ,PS, phosphatidylserine ,ANCAs, anti-neutrophil autoantibodies ,Cell biology ,IgSF, Immunoglobulin superfamily ,Biochemistry ,PH domain, pleckstrin homology domain ,PI(3,4)P2, phosphatidylinositol (3,4)-bisphosphate ,Disease Susceptibility ,Signal transduction ,SNP, single-nucleotide polymorphism ,IP3, inositol triphosphate ,SHIP ,SH2, Src homology 2 ,PMN, polymorphonuclear leukocytes ,Protein Binding ,Signal Transduction ,NETs, neutrophil extracellular traps ,Immunology ,chemical and pharmacologic phenomena ,Biology ,Btk, Bruton's tyrosine kinase ,PE, phosphatidylethanolamine ,Article ,GEF, guanine nucleotide exchange factor ,03 medical and health sciences ,Immune system ,PLC, phospholipase C ,ROS, reactive oxygen species ,ORF, open reading frame ,PKC, protein kinase C ,Animals ,Humans ,ITAM, immunoreceptor tyrosine-based activating motif ,MLCK, myosin light-chain kinase ,Immunoreceptors ,PI3K/AKT/mTOR pathway ,GPCR, G protein-coupled receptor ,G protein-coupled receptor ,DAG, diacyl-glycerol ,ADCC, antibody-dependent cellular cytotoxicity ,MRP8, myeloid-related protein 8 ,ITIM, immunoreceptor tyrosine-based inhibitory motif ,NADPH, nicotinamide adenine dinucleotide phosphate ,ITIM ,Immunity, Innate ,IRAK, interleukin-1 receptor-associated kinase ,Grb2, growth factor receptor-bound protein 2 ,030104 developmental biology ,Gene Expression Regulation ,PI3K, phosphatidylinositol-4,5-bisphosphate 3-kinase ,fMLP, N-Formylmethionine-leucyl-phenylalanine ,MAPK, mitogen-activated protein kinase ,Biomarkers ,030215 immunology ,PIP3, phosphatidylinositol (3,4,5)-trisphosphate - Abstract
Highlights • Neutrophil activities must be tightly controlled to maintain immune homeostasis. • Activating and inhibitory receptors balance the outcome of immune cell activation. • Immunoreceptors contain Ig-like extracellular domains and signal via ITAMs or ITIMs. • Syk or SHP/SHIP mediate downstream signaling after immunoreceptor activation. • Targeting immunoreceptors provides opportunities for therapeutic interventions., Neutrophils play a critical role in the host defense against infection, and they are able to perform a variety of effector mechanisms for this purpose. However, there are also a number of pathological conditions, including autoimmunity and cancer, in which the activities of neutrophils can be harmful to the host. Thus the activities of neutrophils need to be tightly controlled. As in the case of other immune cells, many of the neutrophil effector functions are regulated by a series of immunoreceptors on the plasma membrane. Here, we review what is currently known about the functions of the various individual immunoreceptors and their signaling in neutrophils. While these immunoreceptors allow for the recognition of a diverse range of extracellular ligands, such as cell surface structures (like proteins, glycans and lipids) and extracellular matrix components, they commonly signal via conserved ITAM or ITIM motifs and their associated downstream pathways that depend on the phosphorylation of tyrosine residues in proteins and/or inositol lipids. This allows for a balanced homeostatic regulation of neutrophil effector functions. Given the number of available immunoreceptors and their fundamental importance for neutrophil behavior, it is perhaps not surprising that pathogens have evolved means to evade immune responses through some of these pathways. Inversely, some of these receptors evolved to specifically recognize these pathogens. Finally, some interactions mediated by immunoreceptors in neutrophils have been identified as promising targets for therapeutic intervention.
- Published
- 2016
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