IL-13 signaling in cDC2 is required for systemic anaphylactic responses.

Authors

Yasuyo Harada, Takanori Sasaki, Kazushige Obata-Ninomiya, Takahiro Matsuyama, Satoshi Ueha, Shigeyuki Shichino, Takashi Watanabe, Shuhei Ogawa, Sewon Ki, Yoshie Suzuki, Naoto Ito, Yasutaka Motomura, Hideki Ueno, Steven F Ziegler, Hiromasa Inoue, Peter Burrows, Brian S Kim, Kenneth M Murphy, Masato Kubo

Published in

Proceedings of the National Academy of Sciences of the United States of America. Volume 123. Issue 28. Pages e2608478123. Jul 14, 2026. Epub Jul 09, 2026.

Abstract

Cutaneous allergen sensitization (CAS) is a primary driver of atopic dermatitis (AD) and a key initiator of the "atopic march", which can lead to systemic conditions such as food allergy and anaphylaxis. The type 2 cytokine interleukin-13 (IL-13) is an important regulator of high-affinity IgE antibodies, yet the precise cellular targets and mechanisms by which it orchestrates systemic allergic responses remain incompletely understood. Here, we evaluated the role of IL-13 in a murine CAS model that links skin inflammation to systemic anaphylaxis. Using cell-specific deletions of the IL-13 receptor α1 subunit (Il13ra1), we identify conventional dendritic cells (cDCs), and not T or B cells, as the essential targets of IL-13 for generating high-affinity IgE. Single-cell transcriptomics reveal that IL-13 signaling acts specifically in a cDC2 subset characterized by high expression of CX3CR1, Clec10a (CD301a), and CD301b (Mgl2). Licensing by IL-13 endows these cDC2 with superior antigen-presenting capacity, characterized by the upregulation of MHC class II and costimulatory molecules, including CD301a, CD301b, and ICOSL. These mature cDC2s are mobilized from the periphery to the spleen by a CX3CR1-dependent mechanism, where they are uniquely equipped to induce the differentiation of IL-13-producing T follicular helper (T_FH13) cells. This cascade results in robust germinal center reactions and production of pathogenic, high-affinity IgE. Our findings define an IL-13-cDC2 axis that functions as a critical regulator of the atopic march, providing a mechanistic rationale for the clinical efficacy of IL-13-targeted therapies in allergic diseases.

PMID:
42424420
Bibliographic data and abstract were imported from PubMed on 10 Jul 2026.

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