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ARS Home » Southeast Area » New Orleans, Louisiana » Southern Regional Research Center » Food Processing and Sensory Quality Research » Research » Publications at this Location » Publication #308450
Title: Skin exposure promotes a Th2 - dependent sensitization to peanut allergens

Author
item TORDESILLAS, LETICIA - The Icahn School Of Medicine At Mount Sinai
item GOSWAMI, RITOBRATA - The Icahn School Of Medicine At Mount Sinai
item BENEDÉ-PEREZ, SARA - National Institute Of Environmental Health Sciences (NIEHS, NIH)
item GRISHINA, GALINA - The Icahn School Of Medicine At Mount Sinai
item DUNKIN, DAVID - The Icahn School Of Medicine At Mount Sinai
item JÄRVINEN, KIRSI - Albany Medical College
item Maleki, Soheila
item SAMPSON, HUGH - The Icahn School Of Medicine At Mount Sinai
item BERIN, CECILIA - The Icahn School Of Medicine At Mount Sinai

Submitted to: Journal of Clinical Investigation
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/7/2014
Publication Date: 11/15/2014
Citation: Tordesillas, L., Goswami, R., Benedé-Perez, S., Grishina, G., Dunkin, D., Järvinen, K.M., Maleki, S.J., Sampson, H.A., Berin, C.M. 2014. The skin as a primary site of sensitization to peanut allergens . Journal of Clinical Investigation. 124(11):4965-4975.

Interpretive Summary: Sensitization to foods often occurs in infancy without known prior oral exposure, which suggests that alternative routes of exposure contribute to food allergy. We hypothesized that peanut activates immune pathways in the skin that promote sensitization. We tested this hypothesis by topically exposing mice to allergens on undamaged skin and observed that repeated exposure to peanut led to sensitization and anaphylaxis. Exposure to peanut via the skin induced sensitization to the major peanut allergens, Ara h 1 and Ara h 2, as observed in human peanut allergy. Peanut and Ara h 2 were able to cause an immunological reaction without any additional chemicals mixed in. Peanut directly upregulated immunological signals from human cells and from mouse skin. Peanut also induced alteration in the composition of cells in the skin to cause an allergy-inducing response from specific cells (T cells) of the immune system. Our data support the hypothesis that peanut is a potent food allergen due to inherent immune cell-provoking activity. These results suggest a physiologic mechanism by which skin exposure to food allergens contributes to sensitization to foods in early life.

Technical Abstract: Sensitization to foods often occurs in infancy without known prior oral exposure, which suggests that alternative routes of exposure contribute to food allergy. We hypothesized that peanut activates innate immune pathways in the skin that promote sensitization. We tested this hypothesis by topically exposing mice to allergens on undamaged skin and observed that repeated exposure to peanut led to sensitization and anaphylaxis upon re-challenge. Epicutaneous peanut exposure induced sensitization to the peanut components Ara h 1 and Ara h 2, as observed in human peanut allergy. Peanut and Ara h 2 contained adjuvant activity, shown by induction of bystander sensitization similar to the atopic dermatitis-associated staphylococcal enterotoxin B (SEB). Peanut directly upregulated cytokine expression from human keratinocytes and from mouse skin in vivo, and induced an ST2-dependent alteration in skin-draining dendritic cells to induce Th2 cytokine production from T cells. Our data support the hypothesis that peanut is a potent food allergen due to inherent adjuvant activity. These results suggest a physiologic mechanism by which skin exposure to food allergens contributes to sensitization to foods in early life.