Siglecs in Allergy and Asthma

Overview

Journal Mol Aspects Med

Specialties Biochemistry
Molecular Biology

Date 2022 Jul 14

PMID 35835621

Authors

Bruce S Bochner

Jeremy A OSullivan

Alan T Chang

Bradford A Youngblood

Affiliations

Soon will be listed here.

Abstract

The term "allergic diseases" encompasses several common, IgE-mediated conditions that range from being annoying to those that are life-threatening. Available treatments include active avoidance of the instigating allergen and the use of a variety of oral, inhaled, intranasal, intraocular and injected agents. While most individuals with allergies do well with existing therapies, there are still unmet therapeutic needs. Siglecs (sialic acid-binding, immunoglobulin-like lectins) are a family of single-pass transmembrane I-type lectins found on various subsets of cells, especially those of the immune system. All Siglecs have extracellular domains recognizing sialoside ligands, and most contain cytoplasmic domains with inhibitory signaling activity. This review focuses on Siglecs that likely play a role in regulating allergic and asthmatic responses, and how specific Siglecs, expressed on cells such as eosinophils and mast cells, are being targeted for therapeutic benefit.

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References

Youngblood B, Brock E, Leung J, Falahati R, Bochner B, Rasmussen H . Siglec-8 antibody reduces eosinophils and mast cells in a transgenic mouse model of eosinophilic gastroenteritis. JCI Insight. 2019; 4(19). PMC: 6795394. DOI: 10.1172/jci.insight.126219. View

Galli S, Gaudenzio N, Tsai M . Mast Cells in Inflammation and Disease: Recent Progress and Ongoing Concerns. Annu Rev Immunol. 2020; 38:49-77. DOI: 10.1146/annurev-immunol-071719-094903. View

Kumagai T, Kiwamoto T, Brummet M, Wu F, Aoki K, Zhu Z . Airway glycomic and allergic inflammatory consequences resulting from keratan sulfate galactose 6-O-sulfotransferase (CHST1) deficiency. Glycobiology. 2018; 28(6):406-417. PMC: 5967469. DOI: 10.1093/glycob/cwy025. View

OSullivan J, Chang A, Youngblood B, Bochner B . Eosinophil and mast cell Siglecs: From biology to drug target. J Leukoc Biol. 2020; 108(1):73-81. PMC: 7531194. DOI: 10.1002/JLB.2MR0120-352RR. View

Schleimer R . Immunopathogenesis of Chronic Rhinosinusitis and Nasal Polyposis. Annu Rev Pathol. 2016; 12:331-357. PMC: 5514544. DOI: 10.1146/annurev-pathol-052016-100401. View

Greenberger P, Saltoun C, Grammer L . Northwestern University Allergy-Immunology Syllabus. Allergy Asthma Proc. 2019; 40(6):361. DOI: 10.2500/aap.2019.40.4246. View

Hudson S, Herrmann H, Du J, Cox P, Haddad E, Butler B . Developmental, malignancy-related, and cross-species analysis of eosinophil, mast cell, and basophil siglec-8 expression. J Clin Immunol. 2011; 31(6):1045-53. PMC: 3329870. DOI: 10.1007/s10875-011-9589-4. View

Westermann S, Dietschmann A, Doehler D, Castiglione K, Bochner B, Voehringer D . Siglec-F Promotes IL-33-Induced Cytokine Release from Bone Marrow-Derived Eosinophils Independently of the ITIM and ITIM-like Motif Phosphorylation. J Immunol. 2022; 208(3):732-744. PMC: 8852812. DOI: 10.4049/jimmunol.2100184. View

Camilleri A, Nag S, Russo A, Stiles K, Crystal R, Pagovich O . Gene therapy for a murine model of eosinophilic esophagitis. Allergy. 2021; 76(9):2740-2752. DOI: 10.1111/all.14822. View

10.

Altrichter S, Staubach P, Pasha M, Singh B, Chang A, Bernstein J . An open-label, proof-of-concept study of lirentelimab for antihistamine-resistant chronic spontaneous and inducible urticaria. J Allergy Clin Immunol. 2021; 149(5):1683-1690.e7. DOI: 10.1016/j.jaci.2021.12.772. View

11.

Ben-Baruch Morgenstern N, Ballaban A, Wen T, Shoda T, Caldwell J, Kliewer K . Single-cell RNA sequencing of mast cells in eosinophilic esophagitis reveals heterogeneity, local proliferation, and activation that persists in remission. J Allergy Clin Immunol. 2022; 149(6):2062-2077. PMC: 9177790. DOI: 10.1016/j.jaci.2022.02.025. View

12.

Gonzalez-Gil A, Li T, Porell R, Fernandes S, Tarbox H, Lee H . Isolation, identification, and characterization of the human airway ligand for the eosinophil and mast cell immunoinhibitory receptor Siglec-8. J Allergy Clin Immunol. 2020; 147(4):1442-1452. PMC: 7876160. DOI: 10.1016/j.jaci.2020.08.001. View

13.

Kroezen B, Conti G, Girardi B, Cramer J, Jiang X, Rabbani S . A Potent Mimetic of the Siglec-8 Ligand 6'-Sulfo-Sialyl Lewis. ChemMedChem. 2020; 15(18):1706-1719. DOI: 10.1002/cmdc.202000417. View

14.

Falconer D, Subedi G, Marcella A, Barb A . Antibody Fucosylation Lowers the FcγRIIIa/CD16a Affinity by Limiting the Conformations Sampled by the N162-Glycan. ACS Chem Biol. 2018; 13(8):2179-2189. PMC: 6415948. DOI: 10.1021/acschembio.8b00342. View

15.

Stevens W, Kim T, Pujanauski L, Hao X, Braciale T . Detection and quantitation of eosinophils in the murine respiratory tract by flow cytometry. J Immunol Methods. 2007; 327(1-2):63-74. PMC: 2670191. DOI: 10.1016/j.jim.2007.07.011. View

16.

Tateno H, Crocker P, Paulson J . 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. 2005; 15(11):1125-35. DOI: 10.1093/glycob/cwi097. View

17.

Youngblood B, Brock E, Leung J, Falahati R, Bryce P, Bright J . AK002, a Humanized Sialic Acid-Binding Immunoglobulin-Like Lectin-8 Antibody that Induces Antibody-Dependent Cell-Mediated Cytotoxicity against Human Eosinophils and Inhibits Mast Cell-Mediated Anaphylaxis in Mice. Int Arch Allergy Immunol. 2019; 180(2):91-102. PMC: 6878738. DOI: 10.1159/000501637. View

18.

Patnode M, Cheng C, Chou C, Singer M, Elin M, Uchimura K . Galactose 6-O-sulfotransferases are not required for the generation of Siglec-F ligands in leukocytes or lung tissue. J Biol Chem. 2013; 288(37):26533-45. PMC: 3772201. DOI: 10.1074/jbc.M113.485409. View

19.

Rubinstein E, Cho J, Rosenthal P, Chao J, Miller M, Pham A . Siglec-F inhibition reduces esophageal eosinophilia and angiogenesis in a mouse model of eosinophilic esophagitis. J Pediatr Gastroenterol Nutr. 2011; 53(4):409-16. PMC: 3980963. DOI: 10.1097/MPG.0b013e3182182ff8. View

20.

Bennich H, Ishizaka K, JOHANSSON S, Rowe D, STANWORTH D, TERRY W . Immunoglobulin E: a new class of human immunoglobulin. Immunology. 1968; 15(3):323-4. PMC: 1409482. View