Abstract
Th2 humoral immunity (IgE) is protective against venoms and parasites but detrimental when mounted against innocuous proteins such as food allergens. The generation of IgE immunity toward harmless allergens is initiated at the body barriers (i.e. mucosae and skin) where the allergen and the immune system first meet. Epithelial cytokines (such as TSLP, IL-25, and IL-33), damage-associated molecular patterns (DAMPs), alarmins, or barrier disruption at the time of allergen encounter can deviate dendritic cells (DCs) away from the natural tolerogenic response to a food allergen. Then, instructed DCs migrate to draining lymph nodes and facilitate Th2 CD4 T cell polarization by limiting IL-12p40 production and upregulating costimulatory molecules such as OX40L. In this setting, IL-4 production by CD4 Th2 cells is crucial for the emergence of IgE+ B cells and plasma cells. The lifespan of allergen-specific IgE+ plasma cells is short, thereby limiting their ability to sustain IgE titres over time. In contrast, long-lasting immunological memory that includes CD4 T and B cells is imprinted at the time of sensitization. These cells are activated on allergen exposure and replenish the transient IgE+ plasma cell compartment in an IL-4 dependent manner. While immunological memory provides sustainable immunity against pathogens, it underlies persistence and exacerbation of food allergy. Therefore, reaching a better understanding of Th2 immune memory and the cellular and molecular mechanisms driving IgE-generating secondary responses is a major undertaking in the search for novel therapeutic targets in food allergy.
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Acknowledgements
Research by the Jordana-Waserman lab cited in this work has been supported by the Canadian Institutes of Health Research (CIHR), MedImmune LLC (USA), the National Institutes of Health (NIH, USA), AllerGen NCE, Food Allergy Canada, the Delaney family and the Walter and Maria Schroeder Foundation. MJ is a senior Canada Research Chair in Immunobiology of Respiratory Diseases and Allergy. RJ holds a MITACS Postdoctoral Fellowship. DKC is a Vanier Scholar. We thank Joshua Koenig for critical review of this chapter.
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Jiménez-Saiz, R., Chu, D.K., Waserman, S., Jordana, M. (2017). Initiation, Persistence and Exacerbation of Food Allergy. In: Schmidt-Weber, C. (eds) Allergy Prevention and Exacerbation. Birkhäuser Advances in Infectious Diseases. Springer, Cham. https://doi.org/10.1007/978-3-319-69968-4_7
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