Upregulation of IL-4 Receptor Signaling Pathway in Circulating ILC2s from Asthma Patients

Overview

Journal J Allergy Clin Immunol Glob

Specialty Allergy & Immunology

Date 2023 Oct 2

PMID 37779537

Authors

Rie Baba

Hiroki Kabata

Yoshitaka Shirasaki

Takashi Kamatani

Mai Yamagishi

Misato Irie

Risa Watanabe

Masako Matsusaka

Katsunori Masaki

Jun Miyata

Kazuyo Moro

Sotaro Uemura

Koichi Fukunaga

Affiliations

Soon will be listed here.

Abstract

Background: Group 2 innate lymphoid cells (ILC2s) produce type 2 cytokines by stimulation with epithelial cell-derived cytokines and are implicated in the pathogenesis of various allergic diseases, including asthma. However, differences in the molecular characteristics of ILC2s between patients with asthma and healthy subjects remain unclear.

Objective: We sought to evaluate differences in cytokine production capacity and gene expression profile of ILC2s in the peripheral blood of patients with asthma and healthy subjects.

Methods: We evaluated ILC2s derived from 15 patients with asthma and 7 healthy subjects using flow cytometry, live-cell imaging of secretion activity analysis, and RNA-sequencing.

Results: ILC2s were sorted as CD45LineageCRTH2CD127CD161 cells from the peripheral blood of patients with asthma and healthy subjects, and the number of ILC2s was decreased in patients with asthma (851 ± 1134 vs 2679 ± 3009 cells/20 mL blood; = .0066). However, patient-derived ILC2s were activated to produce more IL-5 and IL-13 in response to stimulation with IL-2, IL-33, and thymic stromal lymphopoietin compared with healthy subject-derived ILC2s ( = .0032 and = .0085, respectively). Furthermore, RNA-sequencing analysis revealed that patient-derived ILC2s had different gene expression profiles, such as increased expression in cell growth-related genes (, , , ), prostaglandin E receptor (), and IL-4 receptor. In addition, a gene set of the IL-4 receptor signaling pathway was significantly upregulated in ILC2s in patients with asthma ( = .042).

Conclusions: Our results suggest that circulating ILC2s in patients with asthma are preactivated via the IL-4 receptor signaling pathway and produce IL-5 and IL-13 vigorously by stimulation.

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