# Atopic skin inflammation promotes systemic anaphylactic responses via IL-13 signaling in conventional dendritic cells

## TL;DR

Skin inflammation in atopic dermatitis can lead to severe allergic reactions through IL-13 signaling in specific immune cells.

## Contribution

The study identifies dendritic cells as key mediators of IgE-mediated anaphylaxis via IL-13 signaling.

## Key findings

- Dendritic cells, not T or B cells, are critical for high-affinity IgE production in anaphylactic responses.
- IL-13 signaling in cDC2s enhances MHC class II and CD301b expression, promoting type 2 immune responses.
- Similar IL-13R-expressing dendritic cells were found in patients with allergic conditions and a history of AD.

## Abstract

Cutaneous allergen sensitization (CAS) underlies atopic dermatitis (AD) and leads to various allergic symptoms, including food allergy and anaphylaxis. IL-13 expression by T follicular helper T (TFH) has been reported to be involved in generating high-affinity IgE antibodies and causing systemic anaphylaxis.1, 2 However, the mechanisms by which IL-13 triggers IgE-mediated allergic responses remain poorly defined. In the present study, we elucidate the role of IL-13 in the CAS-mediated mechanism by which high-affinity IgE antibodies are produced when the same allergen is introduced at a distal site in the secondary sensitization. The CAS model system using mice lacking the cell lineage-specific IL-13 receptor (IL-13R) demonstrated that dendritic cells (DCs), but not T or B cells, are critical in the high-affinity IgE-mediated anaphylactic response. The IL-13 signal in type 2 conventional DCs (cDC2s) enhanced the expression of MHC class II and CD301b, which was essential for the recall of type 2 responses, inducing the production of high-affinity IgE antibodies. Similar IL-13R-expressing DCs were identified in allergic rhinitis and food allergy patients with a history of AD. These findings strongly suggest the importance of DC-specific IL-13 signaling in CAS-induced allergic reactions associated with the atopic march, which is common in human AD patients.