Pru p 3‐Glycodendropeptides Based on Mannoses Promote Changes in the Immunological Properties of Dendritic and T‐Cells from LTP‐Allergic Patients

Abstract

Scope Glycodendropeptides (GDPs) functionalized with mannose can enhance allergen interaction with dendritic cells (DCs) via C‐type lectin receptors (CLRs), modulating the immune response. They can present multiple peptides and have potential applications for diagnosis and treatment of food allergy (FA). The immune response induced by GDPs with mannose and Pru p 3 peptides (mono/tetravalent) with ester (D1ManPrup3/D4ManPrup3) or ether linkers (D1Man‐O‐Prup3/D4Man‐O‐Prup3) in lipid‐transfer‐protein‐allergic patients and tolerant controls is analyzed. Methods and results The immunological response induced by GDPs is studied by assessing monocyte‐derived‐DC maturation, lymphocyte proliferation, cytokine production, and basophil response by flow cytometry. DnManPrup3 was recognized by DCs via CLRs inducing DC maturation in all subjects. However, CCR7 expression is significantly upregulated in allergic patients compared to tolerant controls. These changes correlate with lymphocyte proliferation and specific production of Th2/Th1 cytokines in allergic patients. Moreover, D1ManPrup3 does not induce basophil activation. Conclusion DnManPrup3 induces changes in DC maturation and lymphocyte proliferation, indicating specific recognition via CLRs. Prup3‐GDPs are recognized by immune cells, inducing a specific immune response and modulating the immunological response in FA patients. The specific geometry of D1ManPrup3 in particular makes it a potential candidate for specific immunotherapy development.

Role of nanostructures in allergy: Diagnostics, treatments and safety

“…Moreover, these structures are specifically recognized by LTP‐allergic patients and have the ability to interact with DCs via CLRs, inducing their maturation and promoting the allergen‐specific proliferative response. Additionally, the monomeric compounds that were unable to bridging sIgE on basophil surface do not activate the effector response and produce higher tolerant effects 69 . These promising results indicate that glycodendrimers can be considered as promising adjuvants to be applied in allergy.…”

“…Additionally, the monomeric compounds that were unable to bridging sIgE on basophil surface do not activate the effector response and produce higher tolerant effects. 69 These promising results indicate that glycodendrimers can be considered as promising adjuvants to be applied in allergy.…”

“…At cellular levels, decreased effector cells and inflammatory plasma cells and increased Th1 and regulatory cells have been observed 67 . All these orchestrated by dendritic cells (DCs) that enable the regulation of the altered Th2 response 68 by promoting functional Treg cells 69 …”

New Insights in Therapy for Food Allergy

“…Furthermore, the lower concentration used for the glycosylated nanostructures with Pru p 3 peptides induced a tolerance response, while the higher concentration induced desensitization to peach [ 109 ]. In addition, these Pru p 3 peptide glycosystems promoted changes in the properties of DCs and T Cells and did not activate the basophils from peach allergic patients [ 110 ].…”

Transcriptional changes in dendritic cells underlying allergen specific induced tolerance in a mouse model

“…Multiple studies have demonstrated that these cells are key players in immunomodulation during AIT 9 promoting tolerance, being involved in allergen transport to submandibular lymph nodes, inducing Tregs and reducing allergy symptoms 10 . Our group have demonstrated that the beneficial effects induced by SLIT with Pru p 3 can be orchestrated by DCs, by decreasing costimulatory molecules and migration markers and promoting PD-L1 expression, which is involved in the regulatory response 6 , 11 .…”