# Histamine-induced RPS6 phosphorylation in dendritic cells is associated with the severity of peanut allergic reactions

## TL;DR

This study finds that histamine signaling in dendritic cells after basophil activation increases RPS6 phosphorylation, which is linked to the severity of peanut allergies in adults.

## Contribution

The study identifies a novel age-dependent mechanism linking histamine signaling and RPS6 phosphorylation in dendritic cells to food allergy severity.

## Key findings

- RPS6 phosphorylation in dendritic cells is increased via histamine receptor 2 signaling after IgE-dependent basophil activation.
- In adults, increased RPS6 phosphorylation in conventional DCs correlates with peanut allergy severity.
- This association is not observed in children, suggesting age-dependent differences in allergy mechanisms.

## Abstract

The phosphorylation of the ribosomal protein S6 (RPS6) was reported to be increased in myeloid cell subsets after stimulation with peanut extract in peanut-allergic individuals or with anti-IgE antibodies in both allergic and nonallergic donors. The mechanisms driving this increase of RPS6 phosphorylation (pS6) and its clinical impacts remain to be elucidated. Therefore, we investigated the mechanism of pS6 induction in plasmacytoid DCs (pDCs) and conventional DCs (cDCs) using whole blood stimulated with peanut extract or anti-IgE antibodies. This approach included in vitro basophil depletion and the application of receptor antagonists. Clinical associations with differential pS6 were performed with data from a well-defined cohort of peanut-allergic individuals participating in the food intervention trial TINA. Our findings revealed an increase of pS6 in pDCs and cDCs via histamine receptor 2 (H2R) signaling after IgE-dependent basophil degranulation and histamine release. In adults — but not in children — pS6 in cDCs was positively associated with food allergy severity, as determined by titrated oral food challenges. The association of pS6 in cDCs with food allergy severity in an age-dependent manner suggests a possibly novel functional mechanism, which may contribute to the course of food allergy, e.g., via increased antigen presentation.

<span>RPS6 phosphorylation increases in dendritic cells via histamine signaling after IgE-mediated basophil activation, and correlates in cDCs with food allergy severity in adult allergic individuals</span>