Reframing Fibrosis in Systemic Sclerosis: A Focus on Neutrophil–Macrophage Dynamics

by Katie Dineen, B.S. Biology, Business Development Manager, Preclinical Research Services

A Fresh Lens on Fibrosis in Systemic Sclerosis

Systemic sclerosis (SSc) is a chronic autoimmune disease marked by widespread tissue fibrosis, vasculopathy, and immune activation. While much research has focused on fibroblasts as the end effectors of fibrosis, recent findings are beginning to shift the narrative upstream—to the immune cells that initiate and shape the fibrotic microenvironment.

A 2024 study published in The Journal of Investigative Dermatology adds compelling evidence to this shift. The researchers explored how neutrophils and macrophages—particularly M2-like, pro-fibrotic macrophages—drive the development of fibrosis in SSc. Their findings suggest that manipulating the early innate immune response could have downstream benefits in controlling fibrosis progression.

Neutrophils and M2-Like Macrophages: The Upstream Drivers

The study described how neutrophils, through the formation of neutrophil extracellular traps (NETs), play a key role in promoting the differentiation of macrophages into a fibrosis-promoting M2-like phenotype.
These M2-like macrophages—characterized by high expression of CD206 and low MHCII—were found in abundance in fibrotic skin tissue. They contribute to fibrosis by stimulating TGF-β1, a central pro-fibrotic growth factor. Intriguingly, when neutrophil infiltration was blocked or NETs were enzymatically degraded, both M2-like macrophage presence and TGF-β1 production decreased significantly. The downstream effect? A reduction in skin fibrosis in the SSc model.

These findings underscore a critical neutrophil–macrophage–fibrosis axis and open the door to new therapeutic strategies that intervene early—before fibroblast activation and matrix deposition take hold.

Why This Matters for Preclinical Research

This study reinforces a broader shift in fibrosis research: an increasing recognition that immune cell crosstalk is a fundamental driver of chronic fibrotic disease—not just a byproduct of inflammation.

From a preclinical development standpoint, this means therapeutic programs targeting innate immune signaling, NETs, or macrophage reprogramming need reliable and translational model systems to generate early in vivo and in vitro evidence.

How MLM Medical Labs Supports This Work

At MLM Medical Labs, we’re deeply aligned with this mechanistic direction in fibrosis research. Our capabilities include:

In Vivo Systemic Sclerosis Model

■ Established bleomycin-induced dermal fibrosis model

■ Suitable for investigating immune and stromal mechanisms involved in fibrosis and tissue remodeling

■ Histology, collagen quantification, cytokine analysis, and more

In Vitro Macrophage Polarization Platform

■ Controlled systems for inducing and monitoring M1-to-M2 transitions

■ Flow cytometry and cytokine profiling to assess immune modulation

■ Ideal for immunomodulatory therapies aiming to reduce M2-like fibrotic signaling

Together, these models offer a comprehensive toolkit to explore how immune-modifying therapeutics influence fibrotic processes—bridging mechanistic insight with translational utility.