Targeting IL-33 in Food Allergy: Toward patient stratification.
Monday, March 5, 2018
South Hall A2 (Convention Center)
Erik R. Wambre, PhD, MBE, Nahir Garabatos Leitón, PhD, Veronique Bajzik, Marco Londei, MD, Karen Cerosaletti, PhD, Steven Ziegler, PhD
RATIONALE: Heterogeneity of peanut-specific memory T cell responses could be related to clinical treatment outcomes. Recent findings show that IL-33 can exacerbate Type 2 immune responses through its receptor ST2. However, the functional role of IL-33 in modulating human allergen-specific CD4+ T cell responses remains unclear.

METHODS: Peanut allergic subjects (n=15), aged 6 to 67, were recruited on the basis of clinical history, a serum IgE to peanut of > 0.35 kU/L or positive skin prick test to peanut, and reaction to peanut during oral food challenge. Peanut-specific T-cells were tracked and profiled ex vivo using CD154 upregulation assay in the absence or presence of soluble IL-33. Analyses of surface marker phenotype and the molecular and cytokine profile of these cells was performed to determine the impact of IL-33 in modulating T cell responses to food allergen.

RESULTS: Peanut-reactive T cells fall into two major subsets based on ST2 expression. Expression of ST2 on peanut reactive CD4+ T cells is induced after TCR activation but restricted to the TH2A cell subset (CD27- CRTH2+ CD161+). Interestingly, we observed an increased prevalence of allergen-specific TH2A cells in young peanut allergic subjects compared to adults. Following TCR triggering, IL-33 selectively amplifies pro-inflammatory function of these pathogenic T cells.

CONCLUSIONS: IL-33 is a key regulator of TH2A cell functions and represents an attractive therapeutic target for the treatment of allergic diseases. However, given the complexity of food allergy, stratification of food allergic patients based on their immunotype could enhance immunotherapeutic treatment efficacy.