Sialic acids and autoimmune disease

Immunological Reviews

Volumn 269, Issue 1, 2016, Pages 145-161

  Mahajan, Vinay S ^a,b,c   Pillai, Shiv ^a,b  

^a MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

^b HARVARD MEDICAL SCHOOL   (United States)

^c BRIGHAM AND WOMEN S HOSPITAL   (United States)

Author keywords

Autoimmunity; CD22; CMAH; SIAE; Sialic acids; Siglecs

Indexed keywords

AUTOANTIBODY; CD22 ANTIGEN; CD24 ANTIGEN; COMPLEMENT FACTOR H; ENZYME; IMMUNOGLOBULIN; LECTIN; LIGAND; PROTEIN TYROSINE PHOSPHATASE; SELECTIN; SIALIC ACID; SIALIC ACID BINDING IMMUNOGLOBULIN LIKE LECTIN; SIALIC ACID DERIVATIVE; LYMPHOCYTE ANTIGEN RECEPTOR; N ACETYLNEURAMINIC ACID; SIGLECG PROTEIN, MOUSE;

ADAPTIVE IMMUNITY; ARTICLE; AUTOIMMUNE DISEASE; AUTOIMMUNITY; B LYMPHOCYTE; HEMATOPOIETIC CELL; HOST; HUMAN; IMMUNE RESPONSE; IMMUNE SYSTEM; IMMUNOCOMPETENT CELL; INFLAMMATION; INFLAMMATORY DISEASE; MICROORGANISM; NONHUMAN; PRIORITY JOURNAL; PROTEIN BINDING; ANIMAL; IMMUNOLOGICAL TOLERANCE; IMMUNOLOGY; METABOLISM; MOUSE; PHYSIOLOGY;

ANIMALS; AUTOIMMUNE DISEASES; AUTOIMMUNITY; B-LYMPHOCYTES; HUMANS; IMMUNE TOLERANCE; LECTINS; MICE; N-ACETYLNEURAMINIC ACID; RECEPTORS, ANTIGEN, B-CELL; SIALIC ACID BINDING IG-LIKE LECTIN 2;

EID: 84950129617     PISSN: 01052896     EISSN: 1600065X     Source Type: Journal    
DOI: 10.1111/imr.12344     Document Type: Article

References (134)

1. Schauer R. Sialic acids as regulators of molecular and cellular interactions. Curr Opin Struct Biol 2009;19:507-514.
2. Varki A. Sialic acids in human health and disease. Trends Mol Med 2008;14:351-360.
3. Varki A. Since there are PAMPs and DAMPs, there must be SAMPs? Glycobiology 2011;21:1121-1124.
4. Bianchi ME. DAMPs, PAMPs and alarmins: all we need to know about danger. J Leukoc Biol 2007;81:1-5.
5. Varki A, Gagneux P. Multifarious roles of sialic acids in immunity. Ann N Y Acad Sci 2012;1253:16-36.
6. Vimr ER, Kalivoda KA, Deszo EL, Steenbergen SM. Diversity of microbial sialic acid metabolism. Microbiol Mol Biol Rev 2004;68:132-153.
7. Ang CW, Jacobs BC, Laman JD. The Guillain-Barré syndrome: a true case of molecular mimicry. Trends Immunol 2004;25:61-66.
8. MacAuley MS, Crocker PR, Paulson JC. Siglec-mediated regulation of immune cell function in disease. Nat Rev Immunol 2014;14:653-666.
9. Pillai S, Netravali IA, Cariappa A, Mattoo H. Siglecs and immune regulation. Annu Rev Immunol 2012;30:357-392.
10. Varki A, Angata T. Siglecs-the major subfamily of I-type lectins. Glycobiology 2006;16:1R-27R.
11. Walker JA, Smith KG. CD22: an inhibitory enigma. Immunology 2008;123:314-325.
12. Varki A. Colloquium paper: uniquely human evolution of sialic acid genetics and biology. Proc Natl Acad Sci USA 2010;107(Suppl):8939-8946.
13. Chou HH, et al. Inactivation of CMP-N-acetylneuraminic acid hydroxylase occurred prior to brain expansion during human evolution. Proc Natl Acad Sci USA 2002;99:11736-11741.
14. Angata T, Varki NM, Varki A. A second uniquely human mutation affecting sialic acid biology. J Biol Chem 2001;276:40282-40287.
15. Angata T, Margulies EH, Green ED, Varki A. Large-scale sequencing of the CD33-related Siglec gene cluster in five mammalian species reveals rapid evolution by multiple mechanisms. Proc Natl Acad Sci USA 2004;101:13251-13256.
16. Nguyen DH, Hurtado-Ziola N, Gagneux P, Varki A. Loss of Siglec expression on T lymphocytes during human evolution. Proc Natl Acad Sci USA 2006;103:7765-7770.
17. Varki A. Essentials of Glycobiology. Cold Spring Harbor Laboratory Press {aa}, Plainview, NY, USA, 1999.
18. Klein A, Krishna M, Varki NM, Varki A. 9-O-acetylated sialic acids have widespread but selective expression: analysis using a chimeric dual-function probe derived from influenza C hemagglutinin-esterase. Proc Natl Acad Sci USA 1994;91:7782-7786.
19. 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 2009;206:125-138.
20. Surolia I, et al. Functionally defective germline variants of sialic acid acetylesterase in autoimmunity. Nature 2010;466:243-247.
21. Paulson JC, Macauley MS, Kawasaki N. Siglecs as sensors of self in innate and adaptive immune responses. Ann N Y Acad Sci 2012;1253:37-48.
22. Schwarz F, Fong JJ, Varki A. Human-specific evolutionary changes in the biology of siglecs. Adv Exp Med Biol 2015;842:1-16.
23. Kiwamoto T, Kawasaki N, Paulson JC, Bochner BS. Siglec-8 as a drugable target to treat eosinophil and mast cell-associated conditions. Pharmacol Ther 2012;135:327-336.
24. Angata T. Associations of genetic polymorphisms of Siglecs with human diseases. Glycobiology 2014;24:785-793.
25. Leonard JP, Goldenberg DM. Preclinical and clinical evaluation of epratuzumab (anti-CD22 IgG) in B-cell malignancies. Oncogene 2007;26:3704-3713.
26. Powell LD, Sgroi D, Sjoberg ER, Stamenkovic I, Varki A. Natural ligands of the B cell adhesion molecule CD22 beta carry N-linked oligosaccharides with alpha-2, 6-linked sialic acids that are required for recognition. J Biol Chem 1993;268:7019-7027.
27. Powell LD, Jain RK, Matta KL, Sabesan S, Varki A. Characterization of sialyloligosaccharide binding by recombinant soluble and native cell-associated CD22. Evidence for a minimal structural recognition motif and the potential importance of multisite binding. J Biol Chem 1995;270:7523-7532.
28. Engel P, et al. The same epitope on CD22 of B lymphocytes mediates the adhesion of erythrocytes, T and B lymphocytes, neutrophils, and monocytes. J Immunol 1993;150:4719-4732.
29. Hanasaki K, Varki A, Powell LD. CD22-mediated cell adhesion to cytokine-activated human endothelial cells. Positive and negative regulation by alpha 2-6-sialylation of cellular glycoproteins. J Biol Chem 1995;270:7533-7542.
30. Nitschke L, Carsetti R, Ocker B, Kohler G, Lamers MC. CD22 is a negative regulator of B-cell receptor signalling. Curr Biol 1997;7:133-143.
31. Shaffer AL, et al. Blimp-1 orchestrates plasma cell differentiation by extinguishing the mature B cell gene expression program. Immunity 2002;17:51-62.
32. Leprince C, Draves KE, Geahlen RL, Ledbetter JA, Clark EA. CD22 associates with the human surface IgM-B-cell antigen receptor complex. Proc Natl Acad Sci USA 1993;90:3236-3240.
33. Cornall RJ, et al. Polygenic autoimmune traits: Lyn, CD22, and SHP-1 are limiting elements of a biochemical pathway regulating BCR signaling and selection. Immunity 1998;8:497-508.
34. Smith KG, Tarlinton DM, Doody GM, Hibbs ML, Fearon DT. Inhibition of the B cell by CD22: a requirement for Lyn. J Exp Med 1998;187:807-811.
35. Doody GM, et al. A role in B cell activation for CD22 and the protein tyrosine phosphatase SHP. Science 1995;269:242-244.
36. Lajaunias F, et al. Differentially regulated expression and function of CD22 in activated B-1 and B-2 lymphocytes. J Immunol 2002;168:6078-6083.
37. Gerlach J, et al. B cell defects in SLP65/BLNK-deficient mice can be partially corrected by the absence of CD22, an inhibitory coreceptor for BCR signaling. Eur J Immunol 2003;33:3418-3426.
38. Sato S, Jansen PJ, Tedder TF. CD19 and CD22 expression reciprocally regulates tyrosine phosphorylation of Vav protein during B lymphocyte signaling. Proc Natl Acad Sci USA 1997;94:13158-13162.
39. 2+ signaling. Proc Natl Acad Sci USA 2013;110:12402-12407.
40. Chen J, McLean PA, Neel BG, Okunade G, Shull GE, Wortis HH. CD22 attenuates calcium signaling by potentiating plasma membrane calcium-ATPase activity. Nat Immunol 2004;5:651-657.
41. Wardemann H, Yurasov S, Schaefer A, Young JW, Meffre E, Nussenzweig MC. Predominant autoantibody production by early human B cell precursors. Science 2003;301:1374-1377.
42. Chan VW, Meng F, Soriano P, DeFranco AL, Lowell CA. Characterization of the B lymphocyte populations in Lyn-deficient mice and the role of Lyn in signal initiation and down-regulation. Immunity 1997;7:69-81.
43. Takai T, Ono M, Hikida M, Ohmori H, Ravetch JV. Augmented humoral and anaphylactic responses in Fc gamma RII-deficient mice. Nature 1996;379:346-349.
44. Pao LI, et al. B cell-specific deletion of protein-tyrosine phosphatase Shp1 promotes B-1a cell development and causes systemic autoimmunity. Immunity 2007;27:35-48.
45. Mary C, et al. Dysregulated expression of the Cd22 gene as a result of a short interspersed nucleotide element insertion in Cd22a lupus-prone mice. J Immunol 2000;165:2987-2996.
46. O'Keefe TL, Williams GT, Batista FD, Neuberger MS. Deficiency in CD22, a B cell-specific inhibitory receptor, is sufficient to predispose to development of high affinity autoantibodies. J Exp Med 1999;189:1307-1313.
47. 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 1998;95:7469-7474.
48. Collins BE, Blixt O, DeSieno AR, Bovin N, Marth JD, Paulson JC. Masking of CD22 by cis ligands does not prevent redistribution of CD22 to sites of cell contact. Proc Natl Acad Sci USA 2004;101:6104-6109.
49. Blixt O, Collins BE, van den Nieuwenhof IM, Crocker PR, Paulson JC. Sialoside specificity of the siglec family assessed using novel multivalent probes: identification of potent inhibitors of myelin-associated glycoprotein. J Biol Chem 2003;278:31007-31019.
50. Collins BE, et al. High-affinity ligand probes of CD22 overcome the threshold set by cis ligands to allow for binding, endocytosis, and killing of B cells. J Immunol 2006;177:2994-3003.
51. Han S, Collins BE, Bengtson P, Paulson JC. Homomultimeric complexes of CD22 in B cells revealed by protein-glycan cross-linking. Nat Chem Biol 2005;1:93-97.
52. Harwood NE, Batista FD. The cytoskeleton coordinates the early events of B-cell activation. Cold Spring Harb Perspect Biol 2011;3:a002360.
53. Fujiwara T, Ritchie K, Murakoshi H, Jacobson K, Kusumi A. Phospholipids undergo hop diffusion in compartmentalized cell membrane. J Cell Biol 2002;157:1071-1081.
54. Peaker CJ, Neuberger MS. Association of CD22 with the B cell antigen receptor. Eur J Immunol 1993;23:1358-1363.
55. Poe JC, et al. CD22 regulates B lymphocyte function in vivo through both ligand-dependent and ligand-independent mechanisms. Nat Immunol 2004;5:1078-1087.
56. Zhang M, Varki A. Cell surface sialic acids do not affect primary CD22 interactions with CD45 and surface IgM nor the rate of constitutive CD22 endocytosis. Glycobiology 2004;14:939-949.
57. Ramya TN, et al. In situ trans ligands of CD22 identified by glycan-protein photocross-linking-enabled proteomics. Mol Cell Proteomics 2010;9:1339-1351.
58. Adachi T, et al. CD22 serves as a receptor for soluble IgM. Eur J Immunol 2012;42:241-247.
59. Macauley MS, et al. Antigenic liposomes displaying CD22 ligands induce antigen-specific B cell apoptosis. J Clin Invest 2013;123:3074-3083.
60. Wienands J, Larbolette O, Reth M. Evidence for a preformed transducer complex organized by the B cell antigen receptor. Proc Natl Acad Sci USA 1996;93:7865-7870.
61. Monroe JG. ITAM-mediated tonic signalling through pre-BCR and BCR complexes. Nat Rev Immunol 2006;6:283-294.
62. Hennet T, Chui D, Paulson JC, Marth JD. Immune regulation by the ST6Gal sialyltransferase. Proc Natl Acad Sci USA 1998;95:4504-4509.
63. Collins BE, Smith BA, Bengtson P, Paulson JC. Ablation of CD22 in ligand-deficient mice restores B cell receptor signaling. Nat Immunol 2006;7:199-206.
64. Prescher H, Schweizer A, Kuhfeldt E, Nitschke L, Brossmer R. Discovery of multifold modified sialosides as human CD22/Siglec-2 ligands with nanomolar activity on B-cells. ACS Chem Biol 2014;9:1444-1450.
65. Nitschke L, et al. Expression of aberrant forms of CD22 on B lymphocytes in Cd22a lupus-prone mice affects ligand binding. Int Immunol 2006;18:59-68.
66. Chen GY, et al. Amelioration of sepsis by inhibiting sialidase-mediated disruption of the CD24-SiglecG interaction. Nat Biotechnol 2011;29:428-435.
67. Duong BH, 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 2010;207:173-187.
68. Hoffmann A, et al. Siglec-G is a B1 cell-inhibitory receptor that controls expansion and calcium signaling of the B1 cell population. Nat Immunol 2007;8:695-704.
69. 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 2014;192:2994-3002.
70. Jellusova J, Wellmann U, Amann K, Winkler TH, Nitschke L. CD22 x Siglec-G double-deficient mice have massively increased B1 cell numbers and develop systemic autoimmunity. J Immunol 2010;184:3618-3627.
71. Muller J, et al. Siglec-G deficiency leads to autoimmunity in aging C57BL/6 mice. J Immunol 2015;195:51-60.
72. Hutzler S, et al. The ligand-binding domain of Siglec-G is crucial for its selective inhibitory function on B1 cells. J Immunol 2014;192:5406-5414.
73. Pfrengle F, Macauley MS, Kawasaki N, Paulson JC. Copresentation of antigen and ligands of Siglec-G induces B cell tolerance independent of CD22. J Immunol 2013;191:1724-1731.
74. Macauley MS, Paulson JC. Siglecs induce tolerance to cell surface antigens by BIM-dependent deletion of the antigen-reactive B cells. J Immunol 2014;193:4312-4321.
75. Chang CH, Wang Y, Gupta P, Goldenberg DM. Extensive crosslinking of CD22 by epratuzumab triggers BCR signaling and caspase-dependent apoptosis in human lymphoma cells. mAbs 2015;7:199-211.
76. Sjoberg ER, Powell LD, Klein A, Varki A. Natural ligands of the B cell adhesion molecule CD22 beta can be masked by 9-O-acetylation of sialic acids. J Cell Biol 1994;126:549-562.
77. Varki A. Sialic acids as ligands in recognition phenomena. FASEB J 1997;11:248-255.
78. Shi WX, Chammas R, Varki NM, Powell L, Varki A. Sialic acid 9-O-acetylation on murine erythroleukemia cells affects complement activation, binding to I-type lectins, and tissue homing. J Biol Chem 1996;271:31526-31532.
79. Tiralongo J, Schauer R. The enigma of enzymatic sialic acid O-acetylation. Trends Glycosci Glyc 2004;16:1-15.
80. Vandamme-Feldhaus V, Schauer R. Characterization of the enzymatic 7-O-acetylation of sialic acids and evidence for enzymatic O-acetyl migration from C-7 to C-9 in bovine submandibular gland. J Biochem 1998;124:111-121.
81. Kamerling JP, Schauer R, Shukla AK, Stoll S, Van Halbeek H, Vliegenthart JF. Migration of O-acetyl groups in N, O-acetylneuraminic acids. Eur J Biochem 1987;162:601-607.
82. Arming S, et al. The human Cas1 protein: a sialic acid-specific O-acetyltransferase? Glycobiology 2011;21:553-564.
83. Pillai S, Cariappa A, Pirnie SP. Esterases and autoimmunity: the sialic acid acetylesterase pathway and the regulation of peripheral B cell tolerance. Trends Immunol 2009;30:488-493.
84. Chellappa V, et al. M89V Sialic acid Acetyl Esterase (SIAE) and all other non-synonymous common variants of this gene are catalytically normal. PLoS ONE 2013;8:e53453.
85. Gan EH, MacArthur K, Mitchell AL, Pearce SH. The role of functionally defective rare germline variants of sialic acid acetylesterase in autoimmune Addison's disease. Eur J Endocrinol 2012;167:825-828.
86. Hirschfield GM, et al. Association of primary biliary cirrhosis with variants in the CLEC16A, SOCS1, SPIB and SIAE immunomodulatory genes. Genes Immun 2012;13:328-335.
87. Hunt KA, et al. Rare and functional SIAE variants are not associated with autoimmune disease risk in up to 66, 924 individuals of European ancestry. Nat Genet 2012;44:3-5.
88. Yamamoto M, et al. A missense single-nucleotide polymorphism in the sialic acid acetylesterase (SIAE) gene is associated with anti-PIT-1 antibody syndrome. Endocr J 2014;61:641-644.
89. 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 2007;27:3008-3022.
90. Kelm S, Schauer R, Manuguerra JC, Gross HJ, Crocker PR. Modifications of cell surface sialic acids modulate cell adhesion mediated by sialoadhesin and CD22. Glycoconj J 1994;11:576-585.
91. Hedlund M, et al. N-glycolylneuraminic acid deficiency in mice: implications for human biology and evolution. Mol Cell Biol 2007;27:4340-4346.
92. Kimura N, et al. Human B-lymphocytes express alpha2-6-sialylated 6-sulfo-N-acetyllactosamine serving as a preferred ligand for CD22/Siglec-2. J Biol Chem 2007;282:32200-32207.
93. Banda K, Gregg CJ, Chow R, Varki NM, Varki A. Metabolism of vertebrate amino sugars with N-glycolyl groups: mechanisms underlying gastrointestinal incorporation of the non-human sialic acid xeno-autoantigen N-glycolylneuraminic acid. J Biol Chem 2012;287:28852-28864.
94. Taylor RE, et al. Novel mechanism for the generation of human xeno-autoantibodies against the nonhuman sialic acid N-glycolylneuraminic acid. J Exp Med 2010;207:1637-1646.
95. Pham T, et al. Evidence for a novel human-specific xeno-auto-antibody response against vascular endothelium. Blood 2009;114:5225-5235.
96. Samraj AN, Laubli H, Varki N, Varki A. Involvement of a non-human sialic Acid in human cancer. Front Oncol 2014;4:33.
97. Samraj AN, et al. A red meat-derived glycan promotes inflammation and cancer progression. Proc Natl Acad Sci USA 2015;112:542-547.
98. Padler-Karavani V, et al. Diversity in specificity, abundance, and composition of anti-Neu5Gc antibodies in normal humans: potential implications for disease. Glycobiology 2008;18:818-830.
99. Sinha R, Cross AJ, Graubard BI, Leitzmann MF, Schatzkin A. Meat intake and mortality: a prospective study of over half a million people. Arch Intern Med 2009;169:562-571.
100. Pan A, et al. Red meat consumption and mortality: results from 2 prospective cohort studies. Arch Intern Med 2012;172:555-563.
101. Atkinson JP, Goodship TH. Complement factor H and the hemolytic uremic syndrome. J Exp Med 2007;204:1245-1248.
102. Raychaudhuri S, et al. A rare penetrant mutation in CFH confers high risk of age-related macular degeneration. Nat Genet 2011;43:1232-1236.
103. Shaw PX, et al. Complement factor H genotypes impact risk of age-related macular degeneration by interaction with oxidized phospholipids. Proc Natl Acad Sci USA 2012;109:13757-13762.
104. Pincetic A, et al. Type I and type II Fc receptors regulate innate and adaptive immunity. Nat Immunol 2014;15:707-716.
105. Anthony RM, Nimmerjahn F, Ashline DJ, Reinhold VN, Paulson JC, Ravetch JV. Recapitulation of IVIG anti-inflammatory activity with a recombinant IgG Fc. Science 2008;320:373-376.
106. Fiebiger BM, Maamary J, Pincetic A, Ravetch JV. Protection in antibody- and T cell-mediated autoimmune diseases by antiinflammatory IgG Fcs requires type II FcRs. Proc Natl Acad Sci USA 2015;112:E2385-E2394.
107. Chen GY, Tang J, Zheng P, Liu Y. CD24 and Siglec-10 selectively repress tissue damage-induced immune responses. Science 2009;323:1722-1725.
108. Segura T, Volk MJ, Shea LD. Substrate-mediated DNA delivery: role of the cationic polymer structure and extent of modification. J Control Release 2003;93:69-84.
109. Wang H, et al. HMG-1 as a late mediator of endotoxin lethality in mice. Science 1999;285:248-251.
110. Scaffidi P, Misteli T, Bianchi ME. Release of chromatin protein HMGB1 by necrotic cells triggers inflammation. Nature 2002;418:191-195.
111. Sims GP, Rowe DC, Rietdijk ST, Herbst R, Coyle AJ. HMGB1 and RAGE in inflammation and cancer. Annu Rev Immunol 2010;28:367-388.
112. Tan Y, Zhao M, Xiang B, Chang C, Lu Q. CD24: from a hematopoietic differentiation antigen to a genetic risk factor for multiple autoimmune diseases. Clin Rev Allergy Immunol 2015;PMID: 25666875 [Epub ahead of print].
113. Carl JW Jr, et al. Autoreactive T cells escape clonal deletion in the thymus by a CD24-dependent pathway. J Immunol 2008;181:320-328.
114. Li O, et al. Massive and destructive T cell response to homeostatic cue in CD24-deficient lymphopenic hosts. J Exp Med 2006;203:1713-1720.
115. Tsuboi S, Fukuda M. Roles of O-linked oligosaccharides in immune responses. BioEssays 2001;23:46-53.
116. Cummings RD, Smith DF. The selectin family of carbohydrate-binding proteins: structure and importance of carbohydrate ligands for cell adhesion. BioEssays 1992;14:849-856.
117. Lasky LA. Selectin-carbohydrate interactions and the initiation of the inflammatory response. Annu Rev Biochem 1995;64:113-139.
118. Springer TA. Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell 1994;76:301-314.
119. Yang XD, Karin N, Tisch R, Steinman L, McDevitt HO. Inhibition of insulitis and prevention of diabetes in nonobese diabetic mice by blocking L-selectin and very late antigen 4 adhesion receptors. Proc Natl Acad Sci USA 1993;90:10494-10498.
120. Archelos JJ, Fortwangler T, Hartung HP. Attenuation of experimental autoimmune neuritis in the Lewis rat by treatment with an antibody to L-selectin. Neurosci Lett 1997;235:9-12.
121. Friedline RH, Wong CP, Steeber DA, Tedder TF, Tisch R. L-selectin is not required for T cell-mediated autoimmune diabetes. J Immunol 2002;168:2659-2666.
122. Mora C, Grewal IS, Wong FS, Flavell RA. Role of L-selectin in the development of autoimmune diabetes in non-obese diabetic mice. Int Immunol 2004;16:257-264.
123. Uboldi C, Doring A, Alt C, Estess P, Siegelman M, Engelhardt B. L-Selectin-deficient SJL and C57BL/6 mice are not resistant to experimental autoimmune encephalomyelitis. Eur J Endocrinol 2008;38:2156-2167.
124. Angiari S, et al. TIM-1 glycoprotein binds the adhesion receptor P-selectin and mediates T cell trafficking during inflammation and autoimmunity. Immunity 2014;40:542-553.
125. Angiari S, Constantin G. Regulation of T cell trafficking by the T cell immunoglobulin and mucin domain 1 glycoprotein. Trends Mol Med 2014;20:675-684.
126. Perez-Frias A, et al. Development of an autoimmune syndrome affecting the skin and internal organs in P-selectin glycoprotein ligand 1 leukocyte receptor-deficient mice. Arthritis Rheumatol 2014;66:3178-3189.
127. Varki A. Selectin ligands: will the real ones please stand up? J Clin Invest 1997;100:S31-S35.
128. Rho JH, et al. Discovery of sialyl Lewis A and Lewis X modified protein cancer biomarkers using high density antibody arrays. J Proteomics 2014;96:291-299.
129. Miyara M, et al. Sialyl Lewis x (CD15s) identifies highly differentiated and most suppressive FOXP3high regulatory T cells in humans. Proc Natl Acad Sci USA 2015;112:7225-7230.
130. Ernst B, Magnani JL. From carbohydrate leads to glycomimetic drugs. Nat Rev Drug Discov 2009;8:661-677.
131. Otipoby KL, et al. CD22 regulates thymus-independent responses and the lifespan of B cells. Nature 1996;384:634-637.
132. Sato S, et al. CD22 is both a positive and negative regulator of B lymphocyte antigen receptor signal transduction: altered signaling in CD22-deficient mice. Immunity 1996;5:551-562.
133. Ghosh S, Bandulet C, Nitschke L. Regulation of B cell development and B cell signalling by CD22 and its ligands alpha2, 6-linked sialic acids. Int Immunol 2006;18:603-611.
134. Grewal PK, et al. ST6Gal-I restrains CD22-dependent antigen receptor endocytosis and Shp-1 recruitment in normal and pathogenic immune signaling. Mol Cell Biol 2006;26:4970-4981.