Chemoattractant Receptor-homologous molecule expressed on Th2 cells, or CRTH2, is a receptor found on certain immune cells. It plays a role in regulating immune responses. Understanding CRTH2 provides insight into how the body manages inflammation, particularly in reactions associated with allergies. This receptor influences immune cell functions. Examining its actions helps to clarify its relevance in both health and disease processes.
Understanding CRTH2
CRTH2 is a G-protein coupled receptor, functioning like a “doorbell” on the surface of cells that signals them to act when activated. It is found on specific immune cells, including T helper type 2 (Th2) cells, eosinophils, basophils, and mast cells. These cells participate in allergic and inflammatory responses.
The natural molecule that binds to and activates CRTH2 is prostaglandin D2 (PGD2), a lipid-derived mediator produced by various cells, including mast cells. When PGD2 binds to CRTH2, it initiates cellular responses. This binding translates external signals into specific cellular behaviors, influencing how immune cells respond.
CRTH2’s Role in Immune Regulation
Activation of CRTH2 by PGD2 contributes to inflammatory processes, especially in type 2 immune responses. This activation promotes the directed movement, or chemotaxis, of specific immune cells like Th2 cells, eosinophils, and basophils to sites of inflammation. The accumulation of these cells is a hallmark of allergic and inflammatory conditions.
Upon activation, CRTH2 also enhances the functions of these recruited cells. It can prevent programmed cell death (apoptosis) of Th2 cells and boost their capacity to release inflammatory mediators. These mediators include cytokines such as IL-4, IL-5, and IL-13, which further propagate the inflammatory cascade. This receptor acts as a mediator in immune responses, particularly allergic reactions.
CRTH2 and Allergic Diseases
The involvement of CRTH2 in immune regulation directly links it to several allergic and inflammatory conditions. In allergic asthma, CRTH2 expression is elevated on T cells and eosinophils, contributing to airway inflammation and hyperreactivity. Overactivation of this receptor can exacerbate symptoms like bronchoconstriction and mucus production in the lungs. This pathway helps drive the chronic inflammation seen in many asthma patients.
CRTH2 also plays a role in allergic rhinitis, commonly known as hay fever. Increased CRTH2-positive lymphocytes accumulate in the nasal mucosa, contributing to nasal congestion and inflammation. Similarly, in atopic dermatitis, CRTH2 mRNA expression is high in peripheral blood cells, and circulating eosinophils and T cells show increased surface expression of CRTH2. Dysregulation of CRTH2 can promote the infiltration of Th2 cells and eosinophils into skin lesions, contributing to the characteristic inflammation and itching.
CRTH2 is implicated in chronic rhinosinusitis with nasal polyps, especially the eosinophilic type. Elevated CRTH2 expression in nasal polyps correlates with increased eosinophilic inflammation and a poorer prognosis for recurrence. Its activation contributes to the chemotaxis and activation of immune cells in the nasal passages, maintaining the inflammatory cycle in these conditions. These connections highlight CRTH2 as a factor in the progression and severity of allergic diseases.
Therapeutic Approaches Targeting CRTH2
The understanding of CRTH2’s involvement in allergic and inflammatory pathways has led to the development of new therapeutic strategies. A primary approach uses CRTH2 antagonists, drugs designed to block the receptor’s activity. By preventing PGD2 from binding to CRTH2, these antagonists aim to reduce the recruitment and activation of inflammatory cells, thereby dampening the allergic response.
Several CRTH2 antagonists have undergone clinical investigation for the treatment of asthma and allergic rhinitis. For example, fevipiprant has advanced to later stages of clinical trials for asthma, showing promise in improving lung function in certain patient subgroups. Other antagonists, such as timapiprant and setipiprant, have been studied for their effects in managing allergic rhinitis symptoms.
While some studies have shown beneficial effects, particularly in patients with higher eosinophil counts, the overall clinical benefits of CRTH2 antagonists are still being evaluated. These targeted therapies represent a move towards more specific treatments for allergic diseases, potentially offering more precise anti-inflammatory effects compared to broader medications. The continued research seeks to identify the specific patient populations most likely to benefit from CRTH2 antagonism.