Clinical & Experimental Allergy | Exploring Siglecs: Immune Regulatory Roles in Food Allergy and Therapeutic Potential

This paper systematically reviews the regulatory roles of Siglecs in food allergy-related immune cells and evaluates their feasibility as potential therapeutic targets. It highlights that targeting Siglecs across multiple immune cell types could offer effective prevention or treatment strategies for food allergy, enhancing both therapeutic efficacy and safety.

 

Literature Overview
The article 'Exploring Siglecs: Potential Modulators of Immune Cells in Food Allergy and Therapeutic Applications', published in Clinical & Experimental Allergy, provides a comprehensive review of Siglecs' regulatory functions in food allergy and their potential as therapeutic targets. The paper discusses Siglecs' expression in dendritic cells, T cells, B cells, mast cells, and basophils, along with their signaling pathway modulation mechanisms, particularly in the sensitization and effector phases of food allergy.

Background Knowledge
Siglecs are immunoglobulin-type lectin receptors that recognize sialic acid on cell surfaces and inhibit downstream signaling through SHP-1/2 tyrosine phosphatase recruitment via ITIM domains. Food allergy (FA) involves multiple immune cell types, including dendritic cells (DCs), T cells, B cells, mast cells, and basophils. Current FA management lacks curative treatments and primarily relies on allergen avoidance and emergency interventions, highlighting the urgent need for novel immunotherapeutic strategies. This paper examines Siglecs' expression patterns in immune cells, their modulation of signaling pathways, and the feasibility of inducing immune tolerance through Siglec targeting. It emphasizes that receptors such as Siglec-2, Siglec-3, Siglec-6, Siglec-9, and Siglec-8 may effectively modulate the sensitization or effector phases of FA. However, most studies to date utilize murine models, with limited validation in human systems. Future research requires human cell-based investigations to confirm these findings.

 

 

Research Methods and Experiments
This study employed systematic literature review techniques to analyze Siglecs' expression profiles in food allergy-associated immune cells and their signal transduction mechanisms. Key research focuses included: (1) Siglecs' regulatory roles in dendritic cells, T cells, and B cells during the sensitization phase; (2) Siglecs' influence on mast cell and basophil degranulation in the effector phase; (3) Strategies for inducing immune tolerance through Siglec-targeting approaches using synthetic liposomes or monoclonal antibodies.

Key Conclusions and Perspectives

• Siglecs are broadly expressed across multiple immune cell types, where they suppress FcεRI, TCR, and BCR signaling through ITIM-mediated recruitment of tyrosine phosphatases, thereby reducing cellular activation.
• Targeting Siglec-2 (CD22) in B cells effectively inhibits IgE production, a critical driver of allergic reactions. Synthetic liposomes carrying Siglec-2 ligands and allergens (STALs) demonstrate potential for inducing immune tolerance and lowering sIgE levels.
• Activation of Siglec-3, Siglec-6, Siglec-8, and Siglec-9 in mast cells and basophils suppresses FcεRI signaling, reducing mediator release (e.g., histamine, cytokines) during allergic responses.
• Multi-cell targeting strategies (e.g., simultaneous modulation of Siglecs in B cells and mast cells) may enhance therapeutic efficacy while improving safety and specificity of immune interventions.
• Current findings are predominantly based on murine models; future studies require human cell validation to assess clinical translatability of Siglec-targeting approaches.

Research Significance and Prospects
This work establishes Siglecs as promising therapeutic targets for food allergy, particularly during early sensitization. Targeting Siglecs may enable early intervention to suppress IgE production and mast cell activation. Future research should prioritize development of humanized models to validate clinical translation potential and investigate synergistic effects of multi-Siglec targeting strategies.

 

 

Conclusion
Food allergy represents a global health challenge without curative treatments. This paper systematically summarizes Siglecs' immunoregulatory functions, highlighting their therapeutic potential as immune checkpoint molecules. Findings demonstrate that Siglec-targeting strategies (e.g., Siglec-2, Siglec-3, Siglec-6, Siglec-8, Siglec-9) effectively suppress activation of B cells, T cells, dendritic cells, mast cells, and basophils, thereby mitigating allergic responses. While murine models support these conclusions, further human studies are essential. Development of humanized Siglec-targeting antibodies or synthetic ligands may offer novel immunotherapeutic approaches, with combination Siglec-targeting strategies potentially enhancing efficacy and safety for precision immunotherapy.

 

J S H Schaapherder, K C M Verhoeckx, A M Ehlers, A C Knulst, and L A P M Meulenbroek. Exploring Siglecs: Potential Modulators of Immune Cells in Food Allergy and Therapeutic Applications. Clinical and Experimental Allergy.