No difference in human mast cells derived from peanut allergic versus non-allergic subjects.

Lau F Larsen,E N Clare Mills,Lars K Poulsen,Bettina M Jensen,Nanna Juel‐Berg,Madeleine Rådinger,Ronald Van Ree,Kirsten S Hansen,Anker Hansen

doi:10.1002/iid3.226

Abstract

IntroductionMast cells are the primary effector cells of allergy. This study aimed at characterizing human peripheral blood‐derived mast cells (PBdMC) from peanut allergic and non‐allergic subjects by investigating whether the molecular and stimulus‐response profile of PBdMC discriminate between peanut allergic and healthy individuals.MethodsPBdMC were generated from eight peanut allergic and 10 non‐allergic subjects. The molecular profile (cell surface receptor expression) was assessed using flow cytometry. The stimulus‐response profile (histamine release induced by secretagogues, secretion of cytokines/chemokines and changes in miRNA expression following anti‐IgE activation) was carried out with histamine release test, luminex multiplex assay and miRNA arrays.ResultsExpression of activating receptors (FcϵRI, CD48, CD88, CD117, and C3aR) on PBdMC was not different among peanut allergic and non‐allergic subjects. Likewise, inhibitory receptors (CD32, CD200R, CD300a, and siglec‐8) displayed comparable levels of expression. Both groups of PBdMC were unresponsive to substance P, compound 48/80 and C5a but released comparable levels of histamine when stimulated with anti‐IgE and C3a. Interestingly, among the secreted cytokines/chemokines (IL‐8, IL‐10, IL‐13, IL‐23, IL‐31, IL‐37, MCP‐1, VEGF, GM‐CSF) PBdMC from peanut allergic subjects showed a different secretion pattern of IL‐31 compared to non‐allergic subjects. Investigating miRNA expression from resting or activated PBdMC revealed no significantly difference between peanut allergic and non‐allergic subjects.ConclusionThe molecular and stimulus‐response profile revealed that PBdMC from peanut allergic subjects differently express IL‐31 compared to non‐allergic subjects. However, since only one altered parameter was found among 893 investigated, it is still questionable if the pathophysiological mechanisms of peanut allergy are revealed in PBdMC.

Highlights

Mast cells are the primary effector cells of allergy
Among the secreted cytokines/chemokines (IL-8, IL-10, IL-13, IL23, IL-31, IL-37, MCP-1, VEGF, GM-CSF) peripheral blood-derived mast cells (PBdMC) from peanut allergic subjects showed a different secretion pattern of IL-31 compared to non-allergic subjects
We found that PBdMC can produce GM-CSF, IL-8, IL-10, IL-13, IL-23, IL-31, IL-37, MCP-1, and VEGF (Fig. 3)

Summary

Introduction

This study aimed at characterizing human peripheral blood-derived mast cells (PBdMC) from peanut allergic and non-allergic subjects by investigating whether the molecular and stimulus-response profile of PBdMC discriminate between peanut allergic and healthy individuals. Conclusion: The molecular and stimulus-response profile revealed that PBdMC from peanut allergic subjects differently express IL-31 compared to non-allergic subjects. The primary effector cell of food allergy is the IgE-sensitized tissue-resident mast cell, which, due to its mediator release, cause the clinical symptoms observed during a peanut allergic reaction such as oral swelling and itching, nausea, Mast cells from allergic and healthy subjects stomach cramps, urticaria, diarrhea, hives, and low blood pressure [4]. Peripheral blood-derived mast cells (PBdMC) resemble in vivo human mast cells with respect to morphology, metachromatic stain, FceRI and CD117 expression, histamine release and secretion of chemokines and cytokines upon activation [10, 11]

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