Immunomodulatory Response of Toll-like Receptor Ligand–Peptide Conjugates in Food Allergy

Méndez, Jorge Losada; Palomares, Francisca; Gómez, Francisca; Ramírez‐López, Pedro; Ramos‐Soriano, Javier; Torres, Marı́a José; Mayorga, Cristobalina; Rojo, Javier

doi:10.1021/acschembio.1c00765

Cited by 9 publications

(7 citation statements)

References 69 publications

(149 reference statements)

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“…The sorted ILC2 and T-cells were fixed in PBS containing 1% paraformaldehyde, washed with PBS, stored, and protected from light until analysis. Sub-membrane actin and nuclei (DNA) were labeled with Alexa Fluor 488 Phalloidin (Sigma-Aldrich, Munich, Germany) and Hoechst 33258 (Sigma-Aldrich), respectively ( 32 ). The cells were either transferred to optical-bottom 12-well plates (Thermo Fisher Scientific) in PBS for observation by confocal microscopy ( 32 ).…”

Section: Methodsmentioning

confidence: 99%

“…Sub-membrane actin and nuclei (DNA) were labeled with Alexa Fluor 488 Phalloidin (Sigma-Aldrich, Munich, Germany) and Hoechst 33258 (Sigma-Aldrich), respectively ( 32 ). The cells were either transferred to optical-bottom 12-well plates (Thermo Fisher Scientific) in PBS for observation by confocal microscopy ( 32 ). The samples were analyzed using a Leica DM6000 inverted microscope connected to a Leica SP5 laser scanning confocal system and Fiji software to determine the cell integrity after sorting.…”

Section: Methodsmentioning

confidence: 99%

“…A mean of 1,000 ILC2 was cultured with 25 µg/mL Pru p 3-AF647 ( 27 ) with/without the cocktail cytokines, IL-25/IL-33 (CK) both at 50 ng/mL ( 33 ) (R&D Systems) at 48 h and 37°C, as previously described for Pru p 3 uptake by DCs, as APC ( 32 ). Afterward, ILC2 was fixed and labeled with Alexa Fluor 488 Phalloidin and Hoechst 33258, as previously described ( 32 ). For flow cytometry, ILC2 was acquired in a FACSCanto II Cytometer (BD), and data was analyzed using FlowJo software (BD).…”

Section: Methodsmentioning

confidence: 99%

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Group 2 innate lymphoid cells are key in lipid transfer protein allergy pathogenesis

Palomares,

Pérez-Sánchez,

Nieto

et al. 2024

Front. Immunol.

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BackgroundImmunopathology in food allergy is characterized by an uncontrolled type 2 immune response and specific-IgE production. Recent studies have determined that group 2 innate lymphoid cells (ILC2) participate in the food allergy pathogenic mechanism and their severity. Our objective was to investigate the role of ILC2 in peach-allergic patients due to non-specific lipid transfer protein (Pru p 3) sensitization.MethodsThe immune response in peripheral blood mononuclear cells was characterized in lipid transfer protein-allergic patients and healthy controls. We have analyzed the Pru p 3 uptake on ILC2, the expression of costimulatory molecules, and their involvement on the T-cell proliferative response and cytokine production under different experimental conditions: cytokines involved in group 2 innate lymphoid cell activation (IL-33 and IL-25), Pru p 3 as main food allergen, and the combination of both components (IL-33/IL-25+Pru p 3) using cell sorting, EliSpot, flow cytometry, and confocal microscopy.ResultsOur results show that Pru p 3 allergen is taken up by group 2 innate lymphoid cells, regulating their costimulatory molecule expression (CD83 and HLA-DR) depending on the presence of Pru p 3 and its combination with IL-33/IL-25. The Pru p 3-stimulated ILC2 induced specific GATA3+Th2 proliferation and cytokine (IL-4, IL-5, and IL-13) production in lipid transfer protein-allergic patients in a cell contact-dependent manner with no changes in Tbet+Th1- and FOXP3+Treg cell differentiation.ConclusionsThe results indicate that in lipid transfer protein-allergic patients, the responsible allergen, Pru p 3, interacts with group 2 innate lymphoid cells, promoting a Th2 cell response. Our results might be of interest in vivo, as they show a role of group 2 innate lymphoid cells as antigen-presenting cells, contributing to the development of food allergy. Consequently, group 2 innate lymphoid cells may be considered as potential therapeutic targets.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Group 2 innate lymphoid cells are key in lipid transfer protein allergy pathogenesis

Palomares,

Pérez-Sánchez,

Nieto

et al. 2024

Front. Immunol.

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“…To modulate allergen-specific immune responses, TLR-ligand allergen fusion proteins combining allergens or allergen peptides with an inherent adjuvant activity were proposed and recently reviewed by Blanco-Pérez et al ( Blanco-Pérez et al, 2019 ). Despite promising preclinical data regarding the induction of immunotolerance by the fusion proteins, i.e., for the birch pollen allergen Bet v 1 fused to flagellin, or T cell peptides of the peach LTP Pru p 3 conjugated to TLR7 and TLR4 ligand, so far none of the candidates were clinically evaluated ( Schülke et al, 2010 ; Losada Méndez et al, 2021 ; Goretzki et al, 2022 ).…”

Section: Tlrs In Treatment Of Allergic Diseasesmentioning

confidence: 99%

When the allergy alarm bells toll: The role of Toll-like receptors in allergic diseases and treatment

Wenger,

Grosse-Kathoefer,

Kraiem

et al. 2023

Front. Mol. Biosci.

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Toll-like receptors of the human immune system are specialized pathogen detectors able to link innate and adaptive immune responses. TLR ligands include among others bacteria-, mycoplasma- or virus-derived compounds such as lipids, lipo- and glycoproteins and nucleic acids. Not only are genetic variations in TLR-related genes associated with the pathogenesis of allergic diseases, including asthma and allergic rhinitis, their expression also differs between allergic and non-allergic individuals. Due to a complex interplay of genes, environmental factors, and allergen sources the interpretation of TLRs involved in immunoglobulin E-mediated diseases remains challenging. Therefore, it is imperative to dissect the role of TLRs in allergies. In this review, we discuss i) the expression of TLRs in organs and cell types involved in the allergic immune response, ii) their involvement in modulating allergy-associated or -protective immune responses, and iii) how differential activation of TLRs by environmental factors, such as microbial, viral or air pollutant exposure, results in allergy development. However, we focus on iv) allergen sources interacting with TLRs, and v) how targeting TLRs could be employed in novel therapeutic strategies. Understanding the contributions of TLRs to allergy development allow the identification of knowledge gaps, provide guidance for ongoing research efforts, and built the foundation for future exploitation of TLRs in vaccine design.

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“…New glycosystems functionalized with mannose or fucose and specific ligands combined with Pru p 3 peptides are focused on the modulation of the immune response via C-type lectin receptors (CLRs) [83,84] or Toll-Like Receptors (TLRs) [85]. Regarding this, glycosylated nanostructures combined with immunotherapy, induced long-lasting tolerance with specific transcriptional and methylations changes on DCs [86,87], Treg cells [88] in a peach allergy mouse model.…”

Section: Allergen Immunotherapymentioning

confidence: 99%

Update on In Vitro Diagnostic Tools and Treatments for Food Allergies

Brasal-Prieto,

Fernández-Prades,

Dakhaoui

et al. 2023

Nutrients

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Food allergy (FA) is an adverse immunological reaction to a specific food that can trigger a wide range of symptoms from mild to life-threatening. This adverse reaction is caused by different immunological mechanisms, such as IgE-mediated, non-IgE-mediated and mixed IgE-mediated reactions. Its epidemiology has had a significant increase in the last decade, more so in developed countries. It is estimated that approximately 2 to 10% of the world’s population has FA and this number appears to be increasing and also affecting more children. The diagnosis can be complex and requires the combination of different tests to establish an accurate diagnosis. However, the treatment of FA is based on avoiding the intake of the specific allergenic food, thus being very difficult at times and also controlling the symptoms in case of accidental exposure. Currently, there are other immunomodulatory treatments such as specific allergen immunotherapy or more innovative treatments that can induce a tolerance response. It is important to mention that research in this field is ongoing and clinical trials are underway to assess the safety and efficacy of these different immunotherapy approaches, new treatment pathways are being used to target and promote the tolerance response. In this review, we describe the new in vitro diagnostic tools and therapeutic treatments to show the latest advances in FA management. We conclude that although significant advances have been made to improve therapies and diagnostic tools for FA, there is an urgent need to standardize both so that, in their totality, they help to improve the management of FA.

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Immunomodulatory Response of Toll-like Receptor Ligand–Peptide Conjugates in Food Allergy

Cited by 9 publications

References 69 publications

Group 2 innate lymphoid cells are key in lipid transfer protein allergy pathogenesis

Group 2 innate lymphoid cells are key in lipid transfer protein allergy pathogenesis

When the allergy alarm bells toll: The role of Toll-like receptors in allergic diseases and treatment

Update on In Vitro Diagnostic Tools and Treatments for Food Allergies

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