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Related Experiment Video

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IL-18 receptor axis in allergic conjunctivitis: a multi-omics study.

Liyun Yuan1,2, Wangming Su3, Liangpin Li2

  • 1School of Medicine, Nankai University, Tianjin, China.

Frontiers in Immunology
|January 1, 2026
PubMed
Summary

This study reveals an IL-18 receptor/IFN-γ axis in NK and T cells as a key factor in allergic conjunctivitis (AC) pathophysiology beyond the Th2 model. This finding highlights IL-18R signaling as a potential therapeutic target for AC.

Keywords:
IL-18 receptor axisallergic conjunctivitisgenome-wide association studymucosal immunitysingle-cell RNA sequencing

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Area of Science:

  • Immunology
  • Ophthalmology
  • Genetics

Background:

  • The traditional Th2-centric model inadequately explains allergic conjunctivitis (AC) pathophysiology.
  • Disease heterogeneity in AC suggests involvement of additional immune pathways.
  • Identifying cell-type-specific mechanisms is crucial for understanding AC.

Purpose of the Study:

  • To identify AC-associated candidate genes using human GWAS data.
  • To delineate immune pathways and cell-type-specific mechanisms in AC.
  • To investigate the role of identified genes and pathways in AC pathogenesis.

Main Methods:

  • Integrative multi-omics strategy using FUSION, MAGMA, and UTMOST on human GWAS data.
  • Single-cell RNA sequencing of a mouse model of AC to analyze immune cell communication.
  • Validation in an independent ovalbumin-induced AC mouse model using clinical scoring and molecular analyses.

Main Results:

  • Identified nine high-confidence AC-associated candidate genes, including IL-1 and Toll-like receptor family components.
  • Demonstrated selective upregulation of IL-18 receptor components (Il18r1, Il18rap) in NK and T cells, correlating with interferon-γ (Ifng) expression.
  • Revealed an allergic-state network with enhanced NK cell-linked IFN-γ signaling and altered NF-κB and JAK-STAT pathway activity, validated in an OVA-induced model.

Conclusions:

  • An IL-18 receptor/IFN-γ axis in NK and T cells is a reproducible module associated with AC and its severity.
  • These findings expand the immunopathological framework of AC beyond Th2-driven processes.
  • IL-18R-linked signaling is nominated as a candidate pathway for future mechanistic and therapeutic studies in AC.