Uncontrolled scarring in interstitial lung disease (ILD) leads to irreversible loss of lung function, but scientists don’t yet have a complete understanding of the cellular interactions and molecular signals that drive this process. This knowledge gap has limited the development of therapies that can interrupt disease progression, instead of just slowing fibrosis once it has started.

Ramnik Xavier, MD, PhD

In a recent study led by Alok Jaiswal, PhD, and Ramnik Xavier, MD, PhD, of the Department of Molecular Biology at Mass General Brigham, researchers used a combination of advanced techniques—including single nucleus RNA sequencing, spatial transcriptomics and histopathology—to study lung tissue samples from patients with ILD.

Their goal was to generate a high-resolution map of what’s happening inside fibrotic human lungs to learn how disease-related cell types are organized in space and how their interactions shape fibrotic niches.

They also tested whether the potentially disease‑causing signals identified during this process could trigger harmful changes in human cell‑based lab models. 

The team discovered pockets of active scarring in the lung where damaged repair cells and aggressive scar-forming cells interact. Inflammatory signals misdirected lung cells during repair, while a key molecular regulator called NFATC4 enabled scar‑forming cells to increase scar production.

Together, these findings reveal the complex mechanisms that lock lungs into a cycle of scarring—insights that could lead to new ILD treatments.  

Published in Cell Genomics on January 22, 2026| Read the paper: “Spatial transcriptomics reveals altered communities and drivers of aberrant epithelia and pro-fibrotic fibroblasts in interstitial lung diseases” 

Summary reviewed by: Ramnik Xavier, MD, PhD, senior author