Siglec-mediated regulation of immune cell function in disease

Nature Reviews Immunology

Volumn 14, Issue 10, 2014, Pages 653-666

  MacAuley, Matthew S ^a   Crocker, Paul R ^b   Paulson, James C ^a  

^a SCRIPPS RESEARCH INSTITUTE   (United States)

^b UNIVERSITY OF DUNDEE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

SIALIC ACID BINDING IMMUNOGLOBULIN LIKE LECTIN; N ACETYLNEURAMINIC ACID; POLYSACCHARIDE; PROTEIN BINDING;

ADAPTIVE IMMUNITY; ALLERGIC ASTHMA; ANTIGEN PRESENTING CELL; ANTIGEN SPECIFICITY; AUTOIMMUNE DISEASE; AUTOIMMUNITY; B LYMPHOCYTE; CELL DIFFERENTIATION; CELL FUNCTION; CELL THERAPY; CHRONIC INFLAMMATION; CYTOKINE PRODUCTION; HUMAN; IMMUNOLOGICAL TOLERANCE; IMMUNOPATHOLOGY; IMMUNORECEPTOR TYROSINE BASED ACTIVATION MOTIF; IMMUNORECEPTOR TYROSINE BASED INHIBITION MOTIF; IMMUNOREGULATION; IMMUNOSURVEILLANCE; INFECTION; INNATE IMMUNITY; LEUKEMIA; LYMPHOMA; NEOPLASM; NERVE DEGENERATION; OSTEOCLAST; PNEUMONIA; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN TARGETING; REVIEW; ANIMAL; BIOLOGICAL MODEL; CYTOLOGY; DISEASE PREDISPOSITION; DISEASE RESISTANCE; IMMUNE SYSTEM; IMMUNOLOGY; METABOLISM;

ANIMALS; DISEASE RESISTANCE; DISEASE SUSCEPTIBILITY; HUMANS; IMMUNE SYSTEM; MODELS, IMMUNOLOGICAL; N-ACETYLNEURAMINIC ACID; POLYSACCHARIDES; PROTEIN BINDING; SIALIC ACID BINDING IMMUNOGLOBULIN-LIKE LECTINS;

EID: 84921786419     PISSN: 14741733     EISSN: 14741741     Source Type: Journal    
DOI: 10.1038/nri3737     Document Type: Review

References (149)

1. Crocker, P. R. et al. Sialoadhesin, a macrophage sialic acid binding receptor for haemopoietic cells with 17 immunoglobulin-like domains. EMBO J. 13, 4490-4503 (1994).
2. Sgroi, D., Varki, A., Braesch-Andersen, S., Stamenkovic, I. CD22, a B cell-specific immunoglobulin superfamily member, is a sialic acid-binding lectin. J. Biol. Chem. 268, 7011-7018 (1993).
3. Crocker, P. R., Paulson, J. C., Varki, A. Siglecs and their roles in the immune system. Nature Rev. Immunol. 7, 255-266 (2007).
4. Cao, H. et al. Comparative genomics indicates the mammalian CD33rSiglec locus evolved by an ancient large-scale inverse duplication and suggests all Siglecs share a common ancestral region. Immunogenetics 61, 401-417 (2009).
5. Ali, S. R. et al. Siglec-5 and Siglec-14 are polymorphic paired receptors that modulate neutrophil and amnion signaling responses to group B Streptococcus. J. Exp. Med. 211, 1231-1242 (2014).
6. Cao, H., Crocker, P. R. Evolution of CD33-related siglecs: regulating host immune functions and escaping pathogen exploitation? Immunology 132, 18-26 (2011).
7. Angata, T. et al. Loss of Siglec-14 reduces the risk of chronic obstructive pulmonary disease exacerbation. Cell. Mol. Life Sci. 70, 3199-3210 (2013).
8. Cao, H. et al. SIGLEC16 encodes a DAP12-associated receptor expressed in macrophages that evolved from its inhibitory counterpart SIGLEC11 and has functional and non-functional alleles in humans. Eur. J. Immunol. 38, 2303-2315 (2008).
9. O'Reilly, M. K., Tian, H., Paulson, J. C. CD22 is a recycling receptor that can shuttle cargo between the cell surface and endosomal compartments of B cells. J. Immunol. 186, 1554-1563 (2011).
10. Delputte, P. L. et al. Porcine sialoadhesin (CD169/Siglec-1) is an endocytic receptor that allows targeted delivery of toxins and antigens to macrophages. PLoS ONE 6, e16827 (2011).
11. Kawasaki, N. et al. Targeted delivery of lipid antigen to macrophages via the CD169/sialoadhesin endocytic pathway induces robust invariant natural killer T cell activation. Proc. Natl Acad. Sci. USA 110, 7826-7831 (2013).
12. Stuible, M. et al. Mechanism and function of monoclonal antibodies targeting siglec-15 for therapeutic inhibition of osteoclastic bone resorption. J. Biol. Chem. 289, 6498-6512 (2014).
13. Tateno, H. et al. Distinct endocytic mechanisms of CD22 (Siglec-2) and Siglec-F reflect roles in cell signaling and innate immunity. Mol. Cell. Biol. 27, 5699-5710 (2007).
14. Walter, R. B. et al. ITIM-dependent endocytosis of CD33-related Siglecs: role of intracellular domain, tyrosine phosphorylation, and the tyrosine phosphatases, Shp1 and Shp2. J. Leukoc. Biol. 83, 200-211 (2008).
15. Winterstein, C., Trotter, J., Kramer-Albers, E. M. Distinct endocytic recycling of myelin proteins promotes oligodendroglial membrane remodeling. J. Cell Sci. 121, 834-842 (2008).
16. Attrill, H. et al. Siglec-7 undergoes a major conformational change when complexed with the ?(2, 8)-disialylganglioside GT1b. J. Biol. Chem. 281, 32774-32783 (2006).
17. May, A. P., Robinson, R. C., Vinson, M., Crocker, P. R., Jones, E. Y. Crystal structure of the N-terminal domain of sialoadhesin in complex with 3? sialyllactose at 1.85 A resolution. Mol. Cell 1, 719-728 (1998).
18. Zhuravleva, M. A., Trandem, K., Sun, P. D. Structural implications of Siglec-5-mediated sialoglycan recognition. J. Mol. Biol. 375, 437-447 (2008).
19. Carlin, A. F. et al. Molecular mimicry of host sialylated glycans allows a bacterial pathogen to engage neutrophil Siglec-9 and dampen the innate immune response. Blood 113, 3333-3336 (2009).
20. Pillai, S., Cariappa, A., Pirnie, S. P. Esterases and autoimmunity: the sialic acid acetylesterase pathway and the regulation of peripheral B cell tolerance. Trends Immunol. 30, 488-493 (2009).
21. Klaas, M., Crocker, P. R. Sialoadhesin in recognition of self and non-self. Semin. Immunopathol. 34, 353-364 (2012).
22. Paulson, J. C., Macauley, M. S., Kawasaki, N. Siglecs as sensors of self in innate and adaptive immune responses. Ann. NY Acad. Sci. 1253, 37-48 (2012).
23. Padler-Karavani, V. et al. Rapid evolution of binding specificities and expression patterns of inhibitory CD33-related Siglecs in primates. FASEB J. 28, 1280-1293 (2014).
24. Hutzler, S. et al. The ligand-binding domain of Siglec-G is crucial for its selective inhibitory function on B1 cells. J. Immunol. 192, 5406-5414 (2014).
25. Muller, J. et al. CD22 ligand-binding and signaling domains reciprocally regulate B-cell Ca2+ signaling. Proc. Natl Acad. Sci. USA 110, 12402-12407 (2013).
26. Muller, J., Nitschke, L. The role of CD22 and Siglec-G in B-cell tolerance and autoimmune disease. Nature Rev. Rheumatol. 10, 422-428 (2014).
27. Pillai, S., Netravali, I. A., Cariappa, A., Mattoo, H. Siglecs and immune regulation. Annu. Rev. Immunol. 30, 357-392 (2012).
28. Poe, J. C., Tedder, T. F. CD22 and Siglec-G in B cell function and tolerance. Trends Immunol. 33, 413-420 (2012).
29. Kiwamoto, T., Katoh, T., Tiemeyer, M., Bochner, B. S. The role of lung epithelial ligands for Siglec-8 and Siglec-F in eosinophilic inflammation. Curr. Opin. Allergy Clin. Immunol. 13, 106-111 (2013).
30. Chang, Y. C. et al. Group B Streptococcus engages an inhibitory Siglec through sialic acid mimicry to blunt innate immune and inflammatory responses in vivo. PLoS Pathog. 10, e1003846 (2014).
31. Chang, Y. C., Nizet, V. The interplay between Siglecs and sialylated pathogens. Glycobiology 24, 818-825 (2014).
32. Chang, Y. C., Uchiyama, S., Varki, A., Nizet, V. Leukocyte inflammatory responses provoked by pneumococcal sialidase. mBio 3, e00220-e00211 (2012).
33. Chen, G. Y. et al. Amelioration of sepsis by inhibiting sialidase-mediated disruption of the CD24-SiglecG interaction. Nature Biotech. 29, 428-435 (2011).
34. Chang, Y. C. et al. Role of macrophage sialoadhesin in host defense against the sialylated pathogen group B Streptococcus. J. Mol. Med. http://dx.doi.org/10.1007/s00109-014-1157-y (2014).
35. Klaas, M. et al. Sialoadhesin promotes rapid proinflammatory and type I IFN responses to a sialylated pathogen, Campylobacter jejuni. J. Immunol. 189, 2414-2422 (2012).
36. Ando, M., Tu, W., Nishijima, K., Iijima, S. Siglec-9 enhances IL-10 production in macrophages via tyrosine-based motifs. Biochem. Biophys. Res. Commun. 369, 878-883 (2008).
37. Boyd, C. R. et al. Siglec-E is up-regulated and phosphorylated following lipopolysaccharide stimulation in order to limit TLR-driven cytokine production. J. Immunol. 183, 7703-7709 (2009).
38. Ohta, M. et al. Immunomodulation of monocyte-derived dendritic cells through ligation of tumor-produced mucins to Siglec-9. Biochem. Biophys. Res. Commun. 402, 663-669 (2010).
39. Miyazaki, K. et al. Colonic epithelial cells express specific ligands for mucosal macrophage immunosuppressive receptors siglec-7 and-9. J. Immunol. 188, 4690-4700 (2012).
40. Chen, G. Y., Tang, J., Zheng, P., Liu, Y. CD24 and Siglec-10 selectively repress tissue damage-induced immune responses. Science 323, 1722-1725 (2009).
41. Chen, W. et al. Induction of Siglec-G by RNA viruses inhibits the innate immune response by promoting RIG-I degradation. Cell 152, 467-478 (2013).
42. Avril, T., Wagner, E. R., Willison, H. J., Crocker, P. R. Sialic acid-binding immunoglobulin-like lectin 7 mediates selective recognition of sialylated glycans expressed on Campylobacter jejuni lipooligosaccharides. Infect. Immun. 74, 4133-4141 (2006).
43. Stephenson, H. N. et al. Pseudaminic acid on Campylobacter jejuni flagella modulates dendritic cell IL-10 expression via Siglec-10 receptor: a novel flagellin-host interaction. J. Infect. Dis. http://dx.doi.org/10.1093/infdis/jiu287 (2014).
44. Izquierdo-Useros, N. et al. Siglec-1 is a novel dendritic cell receptor that mediates HIV-1 trans-infection through recognition of viral membrane gangliosides. PLoS Biol. 10, e1001448 (2012).
45. Puryear, W. B. et al. Interferon-inducible mechanism of dendritic cell-mediated HIV-1 dissemination is dependent on Siglec-1/CD169. PLoS Pathog. 9, e1003291 (2013).
46. Zou, Z. et al. Siglecs facilitate HIV-1 infection of macrophages through adhesion with viral sialic acids. PLoS ONE 6, e24559 (2011).
47. Rosenberg, H. F., Dyer, K. D., Foster, P. S. Eosinophils: changing perspectives in health and disease. Nature Rev. Immunol. 13, 9-22 (2013).
48. Pappas, K., Papaioannou, A. I., Kostikas, K., Tzanakis, N. The role of macrophages in obstructive airways disease: chronic obstructive pulmonary disease and asthma. Cytokine 64, 613-625 (2013).
49. Deckers, J., Branco Madeira, F., Hammad, H. Innate immune cells in asthma. Trends Immunol. 34, 540-547 (2013).
50. Caramori, G., Pandit, A., Papi, A. Is there a difference between chronic airway inflammation in chronic severe asthma and chronic obstructive pulmonary disease? Curr. Opin. Allergy Clin. Immunol. 5, 77-83 (2005).
51. Barnes, P. J. Mediators of chronic obstructive pulmonary disease. Pharmacol. Rev. 56, 515-548 (2004).
52. Ilmarinen, P., Kankaanranta, H. Eosinophil apoptosis as a therapeutic target in allergic asthma. Bas. Clin. Pharmacol. Toxicol. 114, 109-117 (2014).
53. Kiwamoto, T., Kawasaki, N., Paulson, J. C., Bochner, B. S. Siglec-8 as a drugable target to treat eosinophil and mast cell-associated conditions. Pharmacol. Ther. 135, 327-336 (2012).
54. Floyd, H. et al. Siglec-8. A novel eosinophil-specific member of the immunoglobulin superfamily. J. Biol. Chem. 275, 861-866 (2000).
55. Zhang, J. Q., Biedermann, B., Nitschke, L., Crocker, P. R. The murine inhibitory receptor mSiglec-E is expressed broadly on cells of the innate immune system whereas mSiglec-F is restricted to eosinophils. Eur. J. Immunol. 34, 1175-1184 (2004).
56. Tateno, H., Crocker, P. R., Paulson, J. C. Mouse Siglec-F and human Siglec-8 are functionally convergent paralogs that are selectively expressed on eosinophils and recognize 6?-sulfo-sialyl Lewis X as a preferred glycan ligand. Glycobiology 15, 1125-1135 (2005).
57. Gao, P. S. et al. Polymorphisms in the sialic acid-binding immunoglobulin-like lectin-8 (Siglec-8) gene are associated with susceptibility to asthma. Eur. J. Hum. Genet. 18, 713-719 (2010).
58. Hudson, S. A., Bovin, N. V., Schnaar, R. L., Crocker, P. R., Bochner, B. S. Eosinophil-selective binding and proapoptotic effect in vitro of a synthetic Siglec-8 ligand, polymeric 6?-sulfated sialyl Lewis X. J. Pharmacol. Exp. Ther. 330, 608-612 (2009).
59. Nutku, E., Aizawa, H., Hudson, S. A., Bochner, B. S. Ligation of Siglec-8: a selective mechanism for induction of human eosinophil apoptosis. Blood 101, 5014-5020 (2003).
60. Nutku-Bilir, E., Hudson, S. A., Bochner, B. S. Interleukin-5 priming of human eosinophils alters siglec-8 mediated apoptosis pathways. Am. J. Respir. Cell. Mol. Biol. 38, 121-124 (2008).
61. Mao, H. et al. Mechanisms of Siglec-F-induced eosinophil apoptosis: a role for caspases but not for SHP-1 Src kinases, NADPH oxidase or reactive oxygen. PLoS ONE 8, e68143 (2013).
62. Kiwamoto, T. et al. Mice deficient in the St3gal3 gene product ?2, 3 sialyltransferase (ST3Gal-III) exhibit enhanced allergic eosinophilic airway inflammation. J. Allergy Clin. Immunol. 133, 240-247 (2014).
63. Bochner, B. S. et al. Glycan array screening reveals a candidate ligand for Siglec-8. J. Biol. Chem. 280, 4307-4312 (2005).
64. Patnode, M. L. et al. Galactose 6-O-sulfotransferases are not required for the generation of Siglec-F ligands in leukocytes or lung tissue. J. Biol. Chem. 288, 26533-26545 (2013).
65. Guo, J. P. et al. Characterization of expression of glycan ligands for Siglec-F in normal mouse lungs. Am. J. Respir. Cell. Mol. Biol. 44, 238-243 (2011).
66. Zhang, M. et al. Defining the in vivo function of Siglec-F, a CD33-related Siglec expressed on mouse eosinophils. Blood 109, 4280-4287 (2007).
67. Cho, J. Y. et al. Chronic OVA allergen challenged Siglec-F deficient mice have increased mucus, remodeling, and epithelial Siglec-F ligands which are up-regulated by IL-4 and IL-13. Respir. Res. 11, 154 (2010).
68. Suzukawa, M. et al. Sialyltransferase ST3Gal-III regulates Siglec-F ligand formation and eosinophilic lung inflammation in mice. J. Immunol. 190, 5939-5948 (2013).
69. McMillan, S. J., Richards, H. E., Crocker, P. R. Siglec-F-dependent negative regulation of allergen-induced eosinophilia depends critically on the experimental model. Immunol. Lett. 160, 11-16 (2014).
70. McMillan, S. J. et al. Siglec-E is a negative regulator of acute pulmonary neutrophil inflammation and suppresses CD11b ?2-integrin-dependent signaling. Blood 121, 2084-2094 (2013).
71. McMillan, S. J., Sharma, R. S., Richards, H. E., Hegde, V., Crocker, P. R. Siglec-E promotes ?2-Integrin-dependent NADPH oxidase activation to suppress neutrophil recruitment to the lung. J. Biol. Chem. 289, 20370-20376 (2014).
72. Wang, J., Shiratori, I., Uehori, J., Ikawa, M., Arase, H. Neutrophil infiltration during inflammation is regulated by PILR? via modulation of integrin activation. Nature Immunol. 14, 34-40 (2013).
73. Kettenmann, H., Hanisch, U. K., Noda, M., Verkhratsky, A. Physiology of microglia. Physiol. Rev. 91, 461-553 (2011).
74. Griciuc, A. et al. Alzheimer's disease risk gene CD33 inhibits microglial uptake of amyloid ?. Neuron 78, 631-643 (2013).
75. Malik, M. et al. CD33 Alzheimer's risk-altering polymorphism, CD33 expression, and exon 2 splicing. J. Neurosci. 33, 13320-13325 (2013).
76. Bradshaw, E. M. et al. CD33 Alzheimer's disease locus: altered monocyte function and amyloid biology. Nature Neurosci. 16, 848-850 (2013).
77. Angata, T. et al. Cloning and characterization of human Siglec-11. A recently evolved signaling molecule that can interact with SHP-1 and SHP-2 and is expressed by tissue macrophages, including brain microglia. J. Biol. Chem. 277, 24466-24474 (2002).
78. Linnartz-Gerlach, B., Kopatz, J., Neumann, H. Siglec functions of microglia. Glycobiology 24, 794-799 (2014).
79. Naj, A. C. et al. Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer's disease. Nature Genet. 43, 436-441 (2011).
80. Hollingworth, P. et al. Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease. Nature Genet. 43, 429-435 (2011).
81. Bertram, L. et al. Genome-wide association analysis reveals putative Alzheimer's disease susceptibility loci in addition to APOE. Am. J. Hum. Genet. 83, 623-632 (2008).
82. Raj, T. et al. CD33: increased inclusion of exon 2 implicates the Ig V-set domain in Alzheimer's disease susceptibility. Hum. Mol. Genet. 23, 2729-2736 (2014).
83. Goodnow, C. C., Sprent, J., Fazekas de St Groth, B., Vinuesa, C. G. Cellular and genetic mechanisms of self tolerance and autoimmunity. Nature 435, 590-597 (2005).
84. Basten, A., Silveira, P. A. B-cell tolerance: mechanisms and implications. Curr. Opin. Immunol. 22, 566-574 (2010).
85. Jellusova, J., Wellmann, U., Amann, K., Winkler, T. H., Nitschke, L. CD22 × Siglec-G double-deficient mice have massively increased B1 cell numbers and develop systemic autoimmunity. J. Immunol. 184, 3618-3627 (2010).
86. Bokers, S. et al. Siglec-G deficiency leads to more severe collagen-induced arthritis and earlier onset of lupus-like symptoms in MRL/lpr mice. J. Immunol. 192, 2994-3002 (2014).
87. Razi, N., Varki, A. Masking and unmasking of the sialic acid-binding lectin activity of CD22 (Siglec-2) on B lymphocytes. Proc. Natl Acad. Sci. USA 95, 7469-7474 (1998).
88. Collins, B. E., Smith, B. A., Bengtson, P., Paulson, J. C. Ablation of CD22 in ligand-deficient mice restores B cell receptor signaling. Nature Immunol. 7, 199-206 (2006).
89. Grewal, P. K. et al. ST6Gal-I restrains CD22-dependent antigen receptor endocytosis and Shp-1 recruitment in normal and pathogenic immune signaling. Mol. Cell. Biol. 26, 4970-4981 (2006).
90. Surolia, I. et al. Functionally defective germline variants of sialic acid acetylesterase in autoimmunity. Nature 466, 243-247 (2010).
91. Naito, Y. et al. Germinal center marker GL7 probes activation-dependent repression of N-glycolylneuraminic acid, a sialic acid species involved in the negative modulation of B-cell activation. Mol. Cell. Biol. 27, 3008-3022 (2007).
92. Cariappa, A. et al. B cell antigen receptor signal strength and peripheral B cell development are regulated by a 9-O-acetyl sialic acid esterase. J. Exp. Med. 206, 125-138 (2009).
93. Kimura, N. et al. Human B-lymphocytes express ?2-6-sialylated 6-sulfo-N-acetyllactosamine serving as a preferred ligand for CD22/Siglec-2. J. Biol. Chem. 282, 32200-32207 (2007).
94. Collins, B. E. et al. Masking of CD22 by cis ligands does not prevent redistribution of CD22 to sites of cell contact. Proc. Natl Acad. Sci. USA 101, 6104-6109 (2004).
95. Lanoue, A., Batista, F. D., Stewart, M., Neuberger, M. S. Interaction of CD22 with ?2, 6-linked sialoglycoconjugates: innate recognition of self to dampen B cell autoreactivity? Eur. J. Immunol. 32, 348-355 (2002).
96. Lee, M. et al. Transcriptional programs of lymphoid tissue capillary and high endothelium reveal novel mechanisms for lymphocyte homing. Nature Immunol. http://dx.doi.org/10.1038/ni2983 (2014).
97. Duong, B. H. et al. Decoration of T-independent antigen with ligands for CD22 and Siglec-G can suppress immunity and induce B cell tolerance in vivo. J. Exp. Med. 207, 173-187 (2010).
98. Pfrengle, F., Macauley, M. S., Kawasaki, N., Paulson, J. C. Copresentation of antigen and ligands of Siglec-G induces B cell tolerance independent of CD22. J. Immunol. 191, 1724-1731 (2013).
99. Macauley, M. S. et al. Antigenic liposomes displaying CD22 ligands induce antigen-specific B cell apoptosis. J. Clin. Invest. 123, 3074-3083 (2013).
100. Courtney, A. H., Puffer, E. B., Pontrello, J. K., Yang, Z. Q., Kiessling, L. L. Sialylated multivalent antigens engage CD22 in trans and inhibit B cell activation. Proc. Natl Acad. Sci. USA 106, 2500-2505 (2009).
101. Adachi, T. et al. CD22 serves as a receptor for soluble IgM. Eur. J. Immunol. 42, 241-247 (2012).
102. Wu, C. et al. Sialoadhesin-positive macrophages bind regulatory T cells, negatively controlling their expansion and autoimmune disease progression. J. Immunol. 182, 6508-6516 (2009).
103. Kidder, D., Richards, H. E., Ziltener, H. J., Garden, O. A., Crocker, P. R. Sialoadhesin ligand expression identifies a subset of CD4+Foxp3-T cells with a distinct activation and glycosylation profile. J. Immunol. 190, 2593-2602 (2013).
104. Bandala-Sanchez, E. et al. T cell regulation mediated by interaction of soluble CD52 with the inhibitory receptor Siglec-10. Nature Immunol. 14, 741-748 (2013).
105. Ricart, A. D. Antibody-drug conjugates of calicheamicin derivative: gemtuzumab ozogamicin and inotuzumab ozogamicin. Clin. Cancer Res. 17, 6417-6427 (2011).
106. Sullivan-Chang, L., O'Donnell, R. T., Tuscano, J. M. Targeting CD22 in B-cell malignancies: current status and clinical outlook. BioDrugs 27, 293-304 (2013).
107. Uckun, F. M., Goodman, P., Ma, H., Dibirdik, I., Qazi, S. CD22 EXON 12 deletion as a pathogenic mechanism of human B-precursor leukemia. Proc. Natl Acad. Sci. USA 107, 16852-16857 (2010).
108. Simonetti, G. et al. Siglec-G deficiency increases susceptibility to develop B-cell lymphoproliferative disorders. Haematologica 99, 1356-1364 (2014).
109. Fuster, M. M., Esko, J. D. The sweet and sour of cancer: glycans as novel therapeutic targets. Nature Rev. Cancer 5, 526-542 (2005).
110. Kumar, V., McNerney, M. E. A new self: MHC-class-I-independent natural-killer-cell self-tolerance. Nature Rev. Immunol. 5, 363-374 (2005).
111. Jandus, C. et al. Interactions between Siglec-7/9 receptors and ligands influence NK cell-dependent tumor immunosurveillance. J. Clin. Invest. 124, 1810-1820 (2014).
112. Hudak, J. E., Canham, S. M., Bertozzi, C. R. Glycocalyx engineering reveals a Siglec-based mechanism for NK cell immunoevasion. Nature Chem. Biol. 10, 69-75 (2014).
113. Nicoll, G. et al. Ganglioside GD3 expression on target cells can modulate NK cell cytotoxicity via siglec-7-dependent and-independent mechanisms. Eur. J. Immunol. 33, 1642-1648 (2003).
114. Belisle, J. A. et al. Identification of Siglec-9 as the receptor for MUC16 on human NK cells, B cells, and monocytes. Mol. Cancer 9, 118 (2010).
115. Toda, M. et al. Ligation of tumour-produced mucins to CD22 dramatically impairs splenic marginal zone B-cells. Biochem. J. 417, 673-683 (2009).
116. O'Reilly, M. K., Paulson, J. C. Siglecs as targets for therapy in immune-cell-mediated disease. Trends Pharmacol. Sci. 30, 240-248 (2009).
117. Chen, W. C. et al. In vivo targeting of B-cell lymphoma with glycan ligands of CD22. Blood 115, 4778-4786 (2010).
118. Chen, W. C. et al. Antigen delivery to macrophages using liposomal nanoparticles targeting sialoadhesin/CD169. PLoS ONE 7, e39039 (2012).
119. Ravandi, F. et al. Gemtuzumab ozogamicin: time to resurrect? J. Clin. Oncol. 30, 3921-3923 (2012).
120. Mims, A., Stuart, R. K. Developmental therapeutics in acute myelogenous leukemia: are there any new effective cytotoxic chemotherapeutic agents out there? Curr. Hematol. Malig. Rep. 8, 156-162 (2013).
121. Farid, S., Mirshafiey, A., Razavi, A. Siglec-8 and Siglec-F, the new therapeutic targets in asthma. Immunopharmacol. Immunotoxicol. 34, 721-726 (2012).
122. Zimmermann, N. et al. Siglec-F antibody administration to mice selectively reduces blood and tissue eosinophils. Allergy 63, 1156-1163 (2008).
123. Kim, Y. H. et al. Antiallergic effect of anti-Siglec-F through reduction of eosinophilic inflammation in murine allergic rhinitis. Am. J. Rhinol. Allergy 27, 187-191 (2013).
124. Rubinstein, E. et al. Siglec-F inhibition reduces esophageal eosinophilia and angiogenesis in a mouse model of eosinophilic esophagitis. J. Pediatr. Gastroenterol. Nutr. 53, 409-416 (2011).
125. Song, D. J. et al. Anti-Siglec-F antibody reduces allergen-induced eosinophilic inflammation and airway remodeling. J. Immunol. 183, 5333-5341 (2009).
126. Chen, W. C., Sigal, D. S., Saven, A., Paulson, J. C. Targeting B lymphoma with nanoparticles bearing glycan ligands of CD22. Leuk. Lymphoma 53, 208-210 (2012).
127. Ooms, K. et al. Evaluation of viral peptide targeting to porcine sialoadhesin using a porcine reproductive and respiratory syndrome virus vaccination-challenge model. Virus Res. 177, 147-155 (2013).
128. Kawasaki, N., Rademacher, C., Paulson, J. C. CD22 regulates adaptive and innate immune responses of B cells. J. Innate Immun. 3, 411-419 (2011).
129. Teitelbaum, S. L. Bone resorption by osteoclasts. Science 289, 1504-1508 (2000).
130. Udagawa, N. et al. Origin of osteoclasts: mature monocytes and macrophages are capable of differentiating into osteoclasts under a suitable microenvironment prepared by bone marrow-derived stromal cells. Proc. Natl Acad. Sci. USA 87, 7260-7264 (1990).
131. Angata, T., Tabuchi, Y., Nakamura, K., Nakamura, M. Siglec-15: an immune system Siglec conserved throughout vertebrate evolution. Glycobiology 17, 838-846 (2007).
132. Hiruma, Y., Hirai, T., Tsuda, E. Siglec-15, a member of the sialic acid-binding lectin, is a novel regulator for osteoclast differentiation. Biochem. Biophys. Res. Commun. 409, 424-429 (2011).
133. Ishida-Kitagawa, N. et al. Siglec-15 protein regulates formation of functional osteoclasts in concert with DNAX-activating protein of 12 kDa (DAP12). J. Biol. Chem. 287, 17493-17502 (2012).
134. Hiruma, Y. et al. Impaired osteoclast differentiation and function and mild osteopetrosis development in Siglec-15-deficient mice. Bone 53, 87-93 (2013).
135. Kameda, Y. et al. Siglec-15 regulates osteoclast differentiation by modulating RANKL-induced phosphatidylinositol 3-Kinase/Akt and Erk pathways in association with signaling adaptor DAP12. J. Bone Miner. Res. 28, 2463-2475 (2013).
136. Silva-Fernandez, L., Rosario, M. P., Martinez-Lopez, J. A., Carmona, L., Loza, E. Denosumab for the treatment of osteoporosis: a systematic literature review. Reumatol Clin. 9, 42-52 (2013).
137. Blixt, O., Collins, B. E., van den Nieuwenhof, I. M., Crocker, P. R., Paulson, J. C. Sialoside specificity of the siglec family assessed using novel multivalent probes: identification of potent inhibitors of myelin-associated glycoprotein. J. Biol. Chem. 278, 31007-31019 (2003).
138. Brinkman-Van der Linden, E. C., Varki, A. New aspects of siglec binding specificities, including the significance of fucosylation and of the sialyl-Tn epitope. Sialic acid-binding immunoglobulin superfamily lectins. J. Biol. Chem. 275, 8625-8632 (2000).
139. Angata, T., Hayakawa, T., Yamanaka, M., Varki, A., Nakamura, M. Discovery of Siglec-14, a novel sialic acid receptor undergoing concerted evolution with Siglec-5 in primates. FASEB J. 20, 1964-1973 (2006).
140. Brinkman-Van der Linden, E. C. et al. Human-specific expression of Siglec-6 in the placenta. Glycobiology 17, 922-931 (2007).
141. Lunnon, K. et al. Systemic inflammation modulates Fc receptor expression on microglia during chronic neurodegeneration. J. Immunol. 186, 7215-7224 (2011).
142. Munday, J. et al. Identification, characterization and leucocyte expression of Siglec-10, a novel human sialic acid-binding receptor. Biochem. J. 355, 489-497 (2001).
143. Toubai, T. et al. Siglec-G-CD24 axis controls the severity of graft-versus-host disease in mice. Blood 123, 3512-3523 (2014).
144. Blasius, A. L., Cella, M., Maldonado, J., Takai, T., Colonna, M. Siglec-H is an IPC-specific receptor that modulates type I IFN secretion through DAP12. Blood 107, 2474-2476 (2006).
145. Puttur, F. et al. Absence of Siglec-H in MCMV infection elevates interferon alpha production but does not enhance viral clearance. PLoS Pathog. 9, e1003648 (2013).
146. Zhang, J. et al. Characterization of Siglec-H as a novel endocytic receptor expressed on murine plasmacytoid dendritic cell precursors. Blood 107, 3600-3608 (2006).
147. Mitra, N. et al. SIGLEC12, a human-specific segregating (pseudo)gene, encodes a signaling molecule expressed in prostate carcinomas. J. Biol. Chem. 286, 23003-23011 (2011).
148. Wang, X. et al. Specific inactivation of two immunomodulatory SIGLEC genes during human evolution. Proc. Natl Acad. Sci. USA 109, 9935-9940 (2012).
149. Macauley, M. S., Paulson, J. C. Siglecs induce tolerance to cell surface antigens by BIM-dependent deletion of the antigen-reactive B cells. J. Immunol. http://dx.doi.org/10.4049/jimmunol.1401723 (2014).