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

• Published in: Frontiers in immunology Vol. 15; p. 1385101
• Main Authors: Palomares, Francisca, Pérez-Sánchez, Natalia, Nieto, Nazaret, Núñez, Rafael, Cañas, José Antonio, Martín-Astorga, María Del Carmen, Cruz-Amaya, Anyith, Torres, María José, Eguíluz-Gracia, Ibon, Mayorga, Cristobalina, Gómez, Francisca
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 25.04.2024
• Subjects: Adult; antigen-presenting cells; Antigens, Plant - immunology; Carrier Proteins - immunology; Cytokines - metabolism; Female; food allergy; Food Hypersensitivity - immunology; Humans; Immunity, Innate; Immunology; innate lymphoid cells; lipid transfers proteins; Lymphocyte Activation - immunology; Lymphocytes - immunology; Lymphocytes - metabolism; Male; Middle Aged; Plant Proteins - immunology; Th2-cells; type 2 immune response; Young Adult; Th2-cells; type 2 immune response; antigen-presenting cells; innate lymphoid cells; food allergy; lipid transfers proteins
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2024.1385101

Immunopathology 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. The 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. Our 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. The 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 , 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.