A positive feedback loop reinforces the allergic immune response in human peanut allergy.

Abstract

Food allergies are a leading cause of anaphylaxis, and cellular mechanisms involving antigen presentation likely play key roles in their pathogenesis. However, little is known about the response of specific antigen-presenting cell (APC) subsets to food allergens in the setting of food allergies. Here, we show that in peanut-allergic humans, peanut allergen drives the differentiation of CD209+ monocyte-derived dendritic cells (DCs) and CD23+ (FcєRII) myeloid dendritic cells through the action of allergen-specific CD4+ T cells. CD209+ DCs act reciprocally on the same peanut-specific CD4+ T cell population to reinforce Th2 cytokine expression in a positive feedback loop, which may explain the persistence of established food allergy. In support of this novel model, we show clinically that the initiation of oral immunotherapy (OIT) in peanut-allergic patients is associated with a decrease in CD209+ DCs, suggesting that breaking the cycle of positive feedback is associated with therapeutic effect.

• Authors: Xiaoying Zhou, Wong Yu, Shu-Chen Lyu, Claudia Macaubas, Bryan Bunning, Ziyuan He, Elizabeth D Mellins, Kari C Nadeau
• Journal: The Journal of experimental medicine (J Exp Med) Vol. 218 Issue 7 (07 05 2021) ISSN: 1540-9538 [Electronic] United States
• PMID: 33944900 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 Zhou et al.

Chemical References

• Allergens
• Cell Adhesion Molecules
• Cytokines
• DC-specific ICAM-3 grabbing nonintegrin
• Lectins, C-Type
• Receptors, Cell Surface
• Receptors, IgE

Topics

• Allergens (immunology)
• Animals
• Antigen-Presenting Cells (immunology)
• Arachis (immunology)
• Cell Adhesion Molecules (immunology)
• Cytokines (immunology)
• Dendritic Cells (immunology)
• Feedback
• Humans
• Immunity (immunology)
• Immunotherapy (methods)
• Lectins, C-Type (immunology)
• Mice
• Monocytes (immunology)
• Peanut Hypersensitivity (immunology)
• Receptors, Cell Surface (immunology)
• Receptors, IgE (immunology)
• T-Lymphocytes, Regulatory (immunology)
• Th2 Cells (immunology)