Integrative Multi-Omics Analysis Characterizes Immune Dysregulation and Altered CD4⁺ Central Memory T-Cell Abundance...

Area of Science:

• Immunology
• Genomics
• Bioinformatics

Background:

• Allergic rhinitis (AR) is a common chronic inflammatory upper airway disease driven by immune dysregulation.
• Understanding the immunomodulatory landscape of AR is crucial for developing targeted therapies.

Purpose of the Study:

• To systematically characterize the immunomodulatory landscape in AR.
• To identify molecular and cellular features linked to immune remodeling in AR.
• To explore potential therapeutic targets for AR.

Main Methods:

• Integrated analysis of bulk transcriptomic and single-cell RNA sequencing data.
• Identification of immunomodulatory-related differentially expressed genes (IMRDEGs) and construction of an immunomodulatory score (IM.Score).
• Machine learning for molecular signature derivation and L1000CDS2 for drug repositioning analysis.

Main Results:

• Identified 12 IMRDEGs and an IM.Score that was lower in AR samples, correlating with distinct immune microenvironments.
• Observed potential reductions in CD4+ central memory T cells and attenuated intercellular communication in AR.
• A six-gene signature showed high performance in training but failed in external validation; identified narciclasine and BRD-K91370081 as potential drug candidates.

Conclusions:

• This multi-omics study highlights coordinated molecular, cellular, and communication alterations in AR.
• The IM.Score, CD4+ central memory T-cell changes, and the six-gene signature are hypothesis-generating findings.
• Further experimental and clinical validation is required for potential diagnostic and therapeutic applications.