The broad goals of the Mechanistic Core are the following: 1) to continue mechanistic studies from the prior granting period aimed at defining the mechanisms underlying the development of food allergy and """"""""natural"""""""" or immunotherapeutically-induced tolerance, 2) to provide a platform for every project within this new proposal to achieve these goals and 3) to utilize the information gathered during the initial granting period to establish new hypotheses and provide new avenues for investigation. During the initial granting period we established uniform reproducible technology across 5 sites allowing for the study of sensitization and T-cell activation, and assessment of the development of tolerance. There were several findings that caused us to question some of the previous dogma including the fact that a large cohort of milk and egg allergic children were already sensitized to peanut at an early age, that the GATA-3 transcription factor may play less of a role in allergic sensitization in humans than previously thought and that there was a high likelihood of a non- T cell origin for IL-4 (and consequent IgE) in these patients. The current proposal seeks to continue the current studies focused on the role of T cells vs. APCs in allergic sensitization and tolerance, as well as expand studies on the role of basophils in this process. In addition, we now plan to specifically explore the expression and regulation of GATA-3 in T and non-T cells, initiate studies attempting to correlate the expression of food allergy as either atopic, i.e. atopic dermatitis, asthma or allergic rhinitis, vs eosinophilic esophagitis using the immunologic parameters previously described, and finally to use a microarray approach to define novel pathways and markers of atopic disease, disease resolution and tolerance and the distinct expression of disease phenotypes (AD vs EE). These ongoing and new studies should enhance our understanding of the pathogenesis of atopic disease based upon human study.
The results of these studies should help us to gain insights into mechanisms of action of three novel immunotherapeutic approaches to treat peanut allergy, allow us to define pathways whereby novel interventions can be approached, and provide insights into mechanisms and biomarkers associated with the natural development and loss of food allergies.
|Martin, Lisa J; He, Hua; Collins, Margaret H et al. (2018) Eosinophilic esophagitis (EoE) genetic susceptibility is mediated by synergistic interactions between EoE-specific and general atopic disease loci. J Allergy Clin Immunol 141:1690-1698|
|Berin, M Cecilia; Grishin, Alexander; Masilamani, Madhan et al. (2018) Egg-specific IgE and basophil activation but not egg-specific T-cell counts correlate with phenotypes of clinical egg allergy. J Allergy Clin Immunol 142:149-158.e8|
|Chehade, Mirna; Jones, Stacie M; Pesek, Robbie D et al. (2018) Phenotypic Characterization of Eosinophilic Esophagitis in a Large Multicenter Patient Population from the Consortium for Food Allergy Research. J Allergy Clin Immunol Pract 6:1534-1544.e5|
|Sampson, Hugh A; Berin, M Cecilia; Plaut, Marshall et al. (2018) The Consortium for Food Allergy Research (CoFAR) The First Generation. J Allergy Clin Immunol :|
|Chiang, David; Chen, Xintong; Jones, Stacie M et al. (2018) Single-cell profiling of peanut-responsive T cells in patients with peanut allergy reveals heterogeneous effector TH2 subsets. J Allergy Clin Immunol 141:2107-2120|
|Watson, C T; Cohain, A T; Griffin, R S et al. (2017) Integrative transcriptomic analysis reveals key drivers of acute peanut allergic reactions. Nat Commun 8:1943|
|Rochman, Mark; Travers, Jared; Miracle, Cora E et al. (2017) Profound loss of esophageal tissue differentiation in patients with eosinophilic esophagitis. J Allergy Clin Immunol 140:738-749.e3|
|Agashe, Charuta; Chiang, David; Grishin, Alexander et al. (2017) Impact of granulocyte contamination on PBMC integrity of shipped blood samples: Implications for multi-center studies monitoring regulatory T cells. J Immunol Methods 449:23-27|
|Schoos, Ann-Marie M; Kattan, Jacob D; Gimenez, Gustavo et al. (2016) Sensitization phenotypes based on protein groups and associations to allergic diseases in children. J Allergy Clin Immunol 137:1277-1280|
|Davis, Benjamin P; Epstein, Tolly; Kottyan, Leah et al. (2016) Association of eosinophilic esophagitis and hypertrophic cardiomyopathy. J Allergy Clin Immunol 137:934-6.e5|
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