Siglecs As Potential Targets of Therapy in Human Mast Cell- And/or Eosinophil-associated Diseases

Overview

Journal Semin Immunol

Specialty Allergy & Immunology

Date 2023 Jul 6

PMID 37413923

Authors

Jeremy A OSullivan

Bradford A Youngblood

Robert P Schleimer

Bruce S Bochner

Affiliations

Soon will be listed here.

Abstract

Siglecs (sialic acid-binding immunoglobulin-like lectins) are a family of vertebrate glycan-binding cell-surface proteins. The majority mediate cellular inhibitory activity once engaged by specific ligands or ligand-mimicking molecules. As a result, Siglec engagement is now of interest as a strategy to therapeutically dampen unwanted cellular responses. When considering allergic inflammation, human eosinophils and mast cells express overlapping but distinct patterns of Siglecs. For example, Siglec-6 is selectively and prominently expressed on mast cells while Siglec-8 is highly specific for both eosinophils and mast cells. This review will focus on a subset of Siglecs and their various endogenous or synthetic sialoside ligands that regulate eosinophil and mast cell function and survival. It will also summarize how certain Siglecs have become the focus of novel therapies for allergic and other eosinophil- and mast cell-related diseases.

Citing Articles

Screening of potential key pathogenic and intervention targets of low-grade glioma based on bioinformatics.

Yi L, Kong W, Jiu Z, Huang Z, Na P, Chen W Transl Cancer Res. 2024; 13(10):5563-5573.

PMID: 39525013 PMC: 11543039. DOI: 10.21037/tcr-24-1662.

Sialylated keratan sulfates on MUC5B are Siglec-8 ligands in the human esophagus.

Li T, Gonzalez-Gil A, Awol A, Ackerman S, Orsburn B, Schnaar R Glycobiology. 2024; 34(10).

PMID: 39173029 PMC: 11364441. DOI: 10.1093/glycob/cwae065.

The origins, manifestations, and potential treatments of allergic disorders.

Vercelli D, Galli S Semin Immunol. 2024; 73:101886.

PMID: 38875768 PMC: 11500650. DOI: 10.1016/j.smim.2024.101886.

Mast cells: a novel therapeutic avenue for cardiovascular diseases?.

Poto R, Marone G, Galli S, Varricchi G Cardiovasc Res. 2024; 120(7):681-698.

PMID: 38630620 PMC: 11135650. DOI: 10.1093/cvr/cvae066.

References

Smiljkovic D, Herrmann H, Sadovnik I, Gamperl S, Berger D, Stefanzl G . Expression and regulation of Siglec-6 (CD327) on human mast cells and basophils. J Allergy Clin Immunol. 2022; 151(1):202-211. DOI: 10.1016/j.jaci.2022.07.018. View

Akin C, Arock M, Valent P . Tyrosine kinase inhibitors for the treatment of indolent systemic mastocytosis: Are we there yet?. J Allergy Clin Immunol. 2022; 149(6):1912-1918. DOI: 10.1016/j.jaci.2022.04.020. View

Kuo B, Li C, Chen J, Shiung Y, Chu C, Lee C . IgE-neutralizing UB-221 mAb, distinct from omalizumab and ligelizumab, exhibits CD23-mediated IgE downregulation and relieves urticaria symptoms. J Clin Invest. 2022; 132(15). PMC: 9337824. DOI: 10.1172/JCI157765. View

Saini S, Rosen K, Hsieh H, Wong D, Conner E, Kaplan A . A randomized, placebo-controlled, dose-ranging study of single-dose omalizumab in patients with H1-antihistamine-refractory chronic idiopathic urticaria. J Allergy Clin Immunol. 2011; 128(3):567-73.e1. DOI: 10.1016/j.jaci.2011.06.010. View

Izumo T, Kuse N, Awano N, Tone M, Jo T, Yoshimura H . Rapid and sustained effects of a single dose of benralizumab on chronic eosinophilic pneumonia. Respir Med Case Rep. 2020; 30:101062. PMC: 7193122. DOI: 10.1016/j.rmcr.2020.101062. View

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

Roufosse F, Kahn J, Rothenberg M, Wardlaw A, Klion A, Kirby S . Efficacy and safety of mepolizumab in hypereosinophilic syndrome: A phase III, randomized, placebo-controlled trial. J Allergy Clin Immunol. 2020; 146(6):1397-1405. PMC: 9579892. DOI: 10.1016/j.jaci.2020.08.037. View

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

Gasser P, Tarchevskaya S, Guntern P, Brigger D, Ruppli R, Zbaren N . The mechanistic and functional profile of the therapeutic anti-IgE antibody ligelizumab differs from omalizumab. Nat Commun. 2020; 11(1):165. PMC: 6949303. DOI: 10.1038/s41467-019-13815-w. View

10.

Wang X, Mitra N, Secundino I, Banda K, Cruz P, Padler-Karavani V . Specific inactivation of two immunomodulatory SIGLEC genes during human evolution. Proc Natl Acad Sci U S A. 2012; 109(25):9935-40. PMC: 3382539. DOI: 10.1073/pnas.1119459109. View

11.

Jackson D, Akuthota P, Roufosse F . Eosinophils and eosinophilic immune dysfunction in health and disease. Eur Respir Rev. 2022; 31(163). PMC: 9489126. DOI: 10.1183/16000617.0150-2021. View

12.

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

13.

Nair P, Wenzel S, Rabe K, Bourdin A, Lugogo N, Kuna P . Oral Glucocorticoid-Sparing Effect of Benralizumab in Severe Asthma. N Engl J Med. 2017; 376(25):2448-2458. DOI: 10.1056/NEJMoa1703501. View

14.

Castro M, Mathur S, Hargreave F, Boulet L, Xie F, Young J . Reslizumab for poorly controlled, eosinophilic asthma: a randomized, placebo-controlled study. Am J Respir Crit Care Med. 2011; 184(10):1125-32. DOI: 10.1164/rccm.201103-0396OC. View

15.

Jennings S, Finnerty C, Hobart J, Martin-Martinez M, Sinclair K, Slee V . Mast Cell Diseases in Practice and Research: Issues and Perspectives Raised by Patients and Their Recommendations to the Scientific Community and Beyond. J Allergy Clin Immunol Pract. 2022; 10(8):2039-2051. DOI: 10.1016/j.jaip.2022.06.018. View

16.

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

17.

Burton O, Stranks A, Tamayo J, Koleoglou K, Schwartz L, Oettgen H . A humanized mouse model of anaphylactic peanut allergy. J Allergy Clin Immunol. 2016; 139(1):314-322.e9. PMC: 5145786. DOI: 10.1016/j.jaci.2016.04.034. View

18.

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

19.

Li Z, Huang Z, Bai L . Cell Interplay in Osteoarthritis. Front Cell Dev Biol. 2021; 9:720477. PMC: 8369508. DOI: 10.3389/fcell.2021.720477. View

20.

OReilly M, Tian H, Paulson J . CD22 is a recycling receptor that can shuttle cargo between the cell surface and endosomal compartments of B cells. J Immunol. 2010; 186(3):1554-63. PMC: 3024466. DOI: 10.4049/jimmunol.1003005. View