Case Study: Multi-Omics Helps Unravel the Genetic Underpinnings of Immune Response

A new study published in Nature Communications sheds light on how genetic differences shape the way immune cells respond to inflammatory signals, offering critical insights into why individuals vary in their susceptibility to infections and inflammatory diseases. The research, led by scientists at the National Institutes of Health (NIH), focused on tissue-resident macrophages (TRMs) in mice and their response to interleukin-4 (IL-4) and bacterial lipopolysaccharide (LPS).

How Studying Macrophages Can Help Us Understand Immune Response

Macrophages, the immune system’s frontline defenders, adapt to signals like cytokines and pathogens through epigenetic and transcriptional reprogramming. Genetic variation between individuals influences this process—particularly in tissue-resident macrophages—but remains poorly understood. The study aimed to uncover why macrophages from different genetic backgrounds (C57BL/6 vs. BALB/c mouse strains) exhibit divergent responses to IL-4 activation and subsequent LPS exposure. 

This work reveals how genetic background shapes immune cell responses at the epigenetic level, explaining why individuals may differ in their ability to combat infections or resolve inflammation. These findings could inform personalized therapies for diseases like sepsis, autoimmune disorders, or chronic infections, where tailored modulation of macrophage activity is critical. 

Arima Genomics’ Role in this Research

The researchers leveraged  Arima Genomics’ Hi-C technology to map 3D genome architecture, revealing how strain-specific chromatin looping and topologically associating domains (TADs) influence enhancer-promoter interactions. The genome-wide chromatin conformation capture (Arima Genomics Hi-C) identified strain-specific looping near IL-4-inducible genes (e.g., Trem2), linking NF-κB motif accessibility to synergistic LPS responses.

The Arima Genomics Hi-C data was combined with RNA-seq, ATAC-seq, and ChIP-seq to build a comprehensive model of genetic and epigenetic regulation. Such multiomic approaches enable researchers to correlate chromatin structure with transcriptional outcomes, demonstrating how genetic variation rewires enhancer landscapes to dictate immune cell behavior. 

Broader Implications for Precision Medicine

This study underscores the importance of understanding genetic diversity in immune responses. By combining cutting-edge technologies like Arima Genomics –Hi-C with single-cell sequencing and functional assays, the authors bridged the gap between genetic variation and immune function—a critical step toward personalizing therapies to account for individual genetic makeup. 

For researchers exploring epigenetic regulation in immunity, Arima Genomics’ solutions offer a powerful tool to dissect how genomic architecture drives cellular responses in health and disease. 

Read the Case Study Here