|Title||Basophil-derived IL-4 promotes epicutaneous antigen sensitization concomitant with the development of food allergy.|
|Publication Type||Journal Article|
|Year of Publication||2017|
|Authors||Hussain, M, Borcard, L, Walsh, KP, Rodriguez, MPena, Mueller, C, Kim, BS, Kubo, M, Artis, D, Noti, M|
|Journal||J Allergy Clin Immunol|
|Date Published||2017 Apr 06|
BACKGROUND: Exaggerated thymic stromal lymphopoietin (TSLP) production and infiltration of basophils are associated with the pathogenesis of atopic dermatitis (AD), a recognized risk factor for the development of food allergies. Although TSLP and basophils have been implicated in promotion of food-induced allergic disorders in response to epicutaneous sensitization, the mechanisms by which TSLP-elicited basophils guide the progression of allergic inflammation in the skin to distant mucosal sites, such as the gastrointestinal tract, are poorly understood.
OBJECTIVE: We sought to test the role of basophil-intrinsic IL-4 production in TH2 sensitization to food antigens in the skin and effector food-induced allergic responses in the gut.
METHODS: Mice were epicutaneously sensitized with ovalbumin on an AD-like skin lesion, followed by intragastric antigen challenge to induce IgE-mediated food allergy. The requirement for basophil-derived IL-4 production for TH2 polarization and the pathogenesis of IgE-mediated food allergy was assessed in vitro by using coculture experiments with naive T cells and in vivo by using Il4 3'UTR mice that selectively lack IL-4 production in basophils.
RESULTS: Epicutaneous food antigen sensitization is associated with infiltration of IL-4-competent innate immune cells to the skin, with basophils and eosinophils representing the predominant populations. In contrast to basophils, absence of eosinophils did not alter disease outcome. Coculture of IL-4-competent basophils together with dendritic cells and naive T cells was sufficient to promote TH2 polarization in an IL-4-dependent manner in vitro, whereas absence of basophil-intrinsic IL-4 production in vivo was associated with reduced food-induced allergic responses.
CONCLUSION: TSLP-elicited basophils promote epicutaneous sensitization to food antigens and subsequent IgE-mediated food allergy through IL-4. Strategies to target the TSLP-basophil-IL-4 axis in patients with AD might lead to innovative therapies that can prevent the progression of allergies to distant mucosal sites.
|Alternate Journal||J. Allergy Clin. Immunol.|