A stylized image of a damaged lung being protected by CRTH2 receptors.

Can a Simple Receptor Hold the Key to Beating Pulmonary Fibrosis?

Beau Callahan in Health & Wellness November 2025 • 4 min read.

"New research unveils the surprising role of CRTH2 in lung inflammation and fibrosis, offering potential pathways for novel treatments."

Pulmonary fibrosis, a relentless and often fatal condition, involves the scarring of lung tissue, making it difficult to breathe and diminishing the quality of life for those affected. While some treatments can slow the progression, a cure remains elusive. Recent research has focused on the complex interplay of inflammation and the body's immune response in driving fibrosis.

A study published in the American Journal of Respiratory Cell and Molecular Biology sheds new light on the role of a specific receptor, CRTH2, in pulmonary inflammation and fibrosis. CRTH2, or chemoattractant receptor homologous molecule expressed on Th2 cells, is known to play a significant role in allergic diseases. The study's findings challenge existing assumptions about its function and offer a potentially new therapeutic angle.

Traditionally, CRTH2 has been associated with promoting inflammation, particularly in conditions like asthma. However, this research reveals a surprising twist: a deficiency in CRTH2 actually worsens bleomycin-induced pulmonary inflammation and fibrosis in mice. This unexpected discovery underscores the intricate nature of the immune system and suggests that CRTH2 may have a protective role in certain contexts.

Why CRTH2 Deficiency Leads to Worsened Lung Conditions

A stylized image of a damaged lung being protected by CRTH2 receptors.

The study, led by Soichiro Ueda and Koichi Fukunaga, investigated the impact of CRTH2 deficiency on bleomycin-induced lung injury in mice. Bleomycin is a chemotherapy drug known to cause pulmonary fibrosis as a side effect, making it a useful tool for studying the disease in animal models. Researchers compared CRTH2-deficient mice (CRTH2-/-) with wild-type mice to assess the effects of CRTH2 absence on lung inflammation and fibrosis.

Contrary to what they expected, the researchers found that CRTH2-/- mice experienced significantly higher mortality rates and exacerbated lung conditions compared to their wild-type counterparts. Specifically, the CRTH2-deficient mice exhibited:

Increased accumulation of inflammatory cells in the lungs.
Reduced lung compliance, indicating stiffer lungs.
Elevated levels of collagen and total protein in the lungs, hallmarks of fibrosis.
Decreased levels of key cytokines like interferon gamma (IFN-γ), IL-6, IL-10, and IL-17A in bronchoalveolar lavage fluid (BALF).

These findings paint a clear picture: the absence of CRTH2 seems to disrupt the body's ability to resolve inflammation and repair damaged lung tissue, leading to a more severe fibrotic response.

A New Direction for Pulmonary Fibrosis Research

The study by Ueda, Fukunaga, and their colleagues opens up exciting new avenues for research into pulmonary fibrosis. By demonstrating the protective role of CRTH2 in the context of bleomycin-induced lung injury, they've challenged the conventional wisdom surrounding this receptor and its role in inflammation. This surprising discovery suggests that targeting CRTH2, perhaps by modulating its activity rather than blocking it entirely, could potentially offer a novel therapeutic strategy for combating pulmonary fibrosis.

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Everything You Need To Know

What is the role of CRTH2 in pulmonary fibrosis, and why is it surprising?

CRTH2, or chemoattractant receptor homologous molecule expressed on Th2 cells, has traditionally been associated with promoting inflammation, especially in allergic diseases like asthma. The surprising part is that research shows a deficiency in CRTH2 actually worsens pulmonary inflammation and fibrosis. This suggests CRTH2 may have a protective role in certain contexts, challenging previous assumptions about its function in lung conditions. The research indicates that the absence of CRTH2 disrupts the body's ability to resolve inflammation and repair damaged lung tissue, leading to a more severe fibrotic response. Further research is needed to fully understand this complex interplay.

How was the protective role of CRTH2 discovered in the context of pulmonary fibrosis research?

The protective role of CRTH2 was discovered through a study using mice and bleomycin, a chemotherapy drug known to induce pulmonary fibrosis. Researchers compared CRTH2-deficient mice (CRTH2-/-) with wild-type mice after administering bleomycin. Unexpectedly, the CRTH2-deficient mice experienced higher mortality rates and exacerbated lung conditions, showing increased inflammation and fibrosis compared to the wild-type mice. This led to the realization that CRTH2 might play a protective role against lung damage in this specific context.

What specific indicators demonstrated that CRTH2 deficiency worsened lung inflammation and fibrosis in the study?

In CRTH2-deficient mice, several key indicators pointed to worsened lung inflammation and fibrosis. These included an increased accumulation of inflammatory cells in the lungs, reduced lung compliance (indicating stiffer lungs), and elevated levels of collagen and total protein in the lungs, which are hallmarks of fibrosis. Additionally, the CRTH2-deficient mice showed decreased levels of key cytokines like interferon gamma (IFN-γ), IL-6, IL-10, and IL-17A in bronchoalveolar lavage fluid (BALF). These factors collectively demonstrated a more severe fibrotic response in the absence of CRTH2.

Given the unexpected protective role of CRTH2, what are the potential new therapeutic strategies for pulmonary fibrosis?

The surprising discovery of CRTH2's protective role suggests that therapeutic strategies might involve modulating CRTH2 activity rather than blocking it entirely, which was the previous approach based on its association with inflammation. This could involve developing drugs that enhance the receptor's beneficial functions in resolving inflammation and promoting tissue repair in the lungs. Instead of using antagonists, future treatments might explore CRTH2 agonists or modulators that fine-tune its activity to achieve a therapeutic effect. Further research is needed to explore how this can be achieved.

What implications does the CRTH2 study have for understanding the relationship between inflammation and pulmonary fibrosis?

The CRTH2 study highlights the complex and context-dependent nature of inflammation in pulmonary fibrosis. It demonstrates that a receptor traditionally thought to promote inflammation can, in certain situations, play a protective role. This suggests that the relationship between inflammation and fibrosis is not always straightforward and that the immune system's response is highly nuanced. The study emphasizes the need for a deeper understanding of specific molecular pathways and their interactions to develop more targeted and effective therapies for pulmonary fibrosis. It also suggests that broad immunosuppressive approaches may not always be the best strategy, as they could potentially disrupt beneficial immune responses mediated by molecules like CRTH2.