Protective Immune Cells Safeguarding Lungs

Unlocking Lung Health: How CRTH2 Research Could Revolutionize Respiratory Treatments

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

"New Research Reveals the Unexpected Role of CRTH2 in Pulmonary Inflammation and Fibrosis, Offering Potential for Innovative Therapies"

Lung diseases, particularly those classified as diffuse parenchymal lung diseases (DPLDs), present a significant challenge to global health. Often referred to as interstitial pneumonia, DPLDs encompass a range of disorders characterized by inflammation and fibrosis—or scarring—of the lung tissue. While some conditions respond to anti-inflammatory treatments like glucocorticoids, others, such as idiopathic pulmonary fibrosis (IPF), do not. This is because IPF involves an inappropriate repair response following lung injury, occurring even in the absence of active inflammation.

Current treatments for IPF, including anti-fibrotic agents like pirfenidone and nintedanib, offer limited effectiveness, underscoring the urgent need for innovative therapeutic strategies. Researchers are actively exploring the complex interplay of chemokines, cytokines, growth factors, and cellular factors that contribute to lung fibrosis. Among these, type 2 cytokines like interleukin (IL-)4, -5, and -13 have garnered significant attention due to their elevated presence in IPF patients.

A recent study sheds new light on the role of CRTH2, a receptor for prostaglandin D2, in the context of bleomycin-induced pulmonary inflammation and fibrosis. The findings challenge previous assumptions and open new avenues for therapeutic intervention. This article delves into the key findings of this study, exploring the implications for future treatments.

What is CRTH2 and Why Does It Matter for Lung Health?

Protective Immune Cells Safeguarding Lungs

CRTH2, or chemoattractant receptor homologous with Th2 cells, is a receptor that responds to prostaglandin D2, a lipid mediator involved in inflammatory processes. Primarily found on Th2 lymphocytes, group 2 innate lymphoid cells, eosinophils, and basophils, CRTH2 influences the production of type 2 cytokines, including IL-13, a known contributor to fibrosis. Because of this association, scientists initially believed that inhibiting CRTH2 might protect against fibrotic lung diseases.

To test this hypothesis, researchers investigated the effects of CRTH2 deficiency in a mouse model of bleomycin-induced lung inflammation and fibrosis. Surprisingly, the CRTH2-deficient mice exhibited worse outcomes compared to their wild-type counterparts, suggesting a protective role for CRTH2 in this context.

Higher mortality rates after bleomycin treatment.
Increased accumulation of inflammatory cells in the lungs.
Reduced pulmonary compliance.
Elevated levels of collagen and total protein in the lungs (indicators of fibrosis).
Decreased levels of interferon γ, IL-6, IL-10, and IL-17A in bronchoalveolar lavage fluid (BALF).

These findings prompted the researchers to explore potential mechanisms behind CRTH2's protective role. Adoptive transfer experiments, where splenocytes (immune cells from the spleen) from wild-type mice were transferred to CRTH2-deficient mice, revealed that the transferred cells could alleviate the inflammation and fibrosis. This suggested that specific hematopoietic cells within the spleen, expressing CRTH2, were responsible for the protective effect.

The Future of CRTH2 Research in Lung Disease

While the study's findings are unexpected, they underscore the complex nature of lung diseases and highlight the potential of CRTH2 as a therapeutic target. Further research is needed to fully elucidate the mechanisms by which CRTH2 exerts its protective effects, potentially leading to the development of novel treatments for pulmonary inflammation and fibrosis. These advances are particularly relevant for conditions like IPF, where current therapeutic options remain limited.

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Everything You Need To Know

What is CRTH2 and where is it typically found in the body?

CRTH2, which stands for chemoattractant receptor homologous with Th2 cells, is a receptor that responds to prostaglandin D2, a lipid mediator involved in inflammatory processes. It is primarily found on Th2 lymphocytes, group 2 innate lymphoid cells, eosinophils, and basophils. Its location on these cells means it directly influences the production of type 2 cytokines, such as IL-13, a known contributor to fibrosis. Understanding CRTH2's presence on these specific immune cells is crucial for deciphering its complex role in lung diseases.

How was CRTH2 initially thought to affect lung fibrosis, and what did recent research surprisingly reveal about its actual role?

Initially, because CRTH2 influences the production of type 2 cytokines like IL-13, which promotes fibrosis, it was thought that inhibiting CRTH2 might protect against fibrotic lung diseases. However, recent research using a mouse model of bleomycin-induced lung inflammation and fibrosis surprisingly revealed that CRTH2-deficient mice exhibited worse outcomes compared to wild-type mice. This suggests that CRTH2 may have a protective role in this context, challenging previous assumptions about its involvement in pulmonary fibrosis.

What were the key findings in the study that indicated a potential protective role for CRTH2 in lung inflammation and fibrosis?

The key findings that suggested a protective role for CRTH2 included higher mortality rates in CRTH2-deficient mice after bleomycin treatment, increased accumulation of inflammatory cells in the lungs, reduced pulmonary compliance, elevated levels of collagen and total protein (indicators of fibrosis), and decreased levels of interferon γ, IL-6, IL-10, and IL-17A in bronchoalveolar lavage fluid (BALF). These results collectively indicated that CRTH2 deficiency exacerbated lung inflammation and fibrosis, rather than alleviating it.

How did adoptive transfer experiments help researchers understand the mechanism behind CRTH2's protective effects in the lungs?

Adoptive transfer experiments involved transferring splenocytes (immune cells from the spleen) from wild-type mice to CRTH2-deficient mice. These experiments revealed that the transferred cells could alleviate the inflammation and fibrosis in the recipient mice. This suggested that specific hematopoietic cells within the spleen, expressing CRTH2, were responsible for the protective effect. These experiments highlighted the importance of CRTH2-expressing immune cells in modulating the inflammatory response and fibrosis in the lungs.

Given the unexpected findings about CRTH2, what are the future implications for research and potential treatments for lung diseases like idiopathic pulmonary fibrosis (IPF)?

The unexpected findings about CRTH2 underscore the complex nature of lung diseases and highlight the potential of CRTH2 as a therapeutic target, albeit in a more nuanced way than previously thought. Further research is needed to fully elucidate the mechanisms by which CRTH2 exerts its protective effects. These advances are particularly relevant for conditions like IPF, where current therapeutic options remain limited. Future treatments may involve modulating CRTH2 activity to promote its protective functions, rather than simply inhibiting it, which could open new avenues for therapeutic intervention in pulmonary inflammation and fibrosis.