College
College of Arts and Sciences
Mentor Information
Stuart Maudsley, PhD
Description
Immune and inflammatory disorders occur when the immune system becomes overactive, leading to ongoing inflammation and tissue damage. The β2-adrenergic receptor (β2-AR), found on many immune cells, helps regulate how immune cells move and respond. Traditional β2-AR drugs activate multiple signaling pathways at the same time, which can lead to inconsistent effects and off-target side effects such as increased heart rate, tremors, and reduced receptor sensitivity over time. This highlights the need for more targeted approaches. This systematic review examined whether biased agonism of β2-AR can selectively activate specific signaling pathways to better control immune responses and improve treatment outcomes. A three-week PubMed search identified relevant studies using the terms biased agonism, β2-AR, immune dysregulation, and inflammation. Five independent reviewers screened 150 peer-reviewed, English-language studies. Studies were included if they compared selective versus non-selective receptor activation and reported measurable signaling or treatment outcomes. After exclusions, 60 studies were included in the final analysis. Across recent studies, biased β2-AR activation produced more targeted signaling than traditional approaches. β-arrestin-biased ligands preferentially activated pathways involved in receptor regulation and immune signaling. Treatment effects varied across studies, suggesting outcomes depend on disease type and patient context. Overall, biased β2-AR agonism offers a more precise approach to immune regulation with the potential to reduce cardiovascular and systemic side effects, supporting continued development of targeted therapies for inflammatory disorders.
Biased Agonism at β2-Adrenergic Receptor for Therapeutic Precision
Immune and inflammatory disorders occur when the immune system becomes overactive, leading to ongoing inflammation and tissue damage. The β2-adrenergic receptor (β2-AR), found on many immune cells, helps regulate how immune cells move and respond. Traditional β2-AR drugs activate multiple signaling pathways at the same time, which can lead to inconsistent effects and off-target side effects such as increased heart rate, tremors, and reduced receptor sensitivity over time. This highlights the need for more targeted approaches. This systematic review examined whether biased agonism of β2-AR can selectively activate specific signaling pathways to better control immune responses and improve treatment outcomes. A three-week PubMed search identified relevant studies using the terms biased agonism, β2-AR, immune dysregulation, and inflammation. Five independent reviewers screened 150 peer-reviewed, English-language studies. Studies were included if they compared selective versus non-selective receptor activation and reported measurable signaling or treatment outcomes. After exclusions, 60 studies were included in the final analysis. Across recent studies, biased β2-AR activation produced more targeted signaling than traditional approaches. β-arrestin-biased ligands preferentially activated pathways involved in receptor regulation and immune signaling. Treatment effects varied across studies, suggesting outcomes depend on disease type and patient context. Overall, biased β2-AR agonism offers a more precise approach to immune regulation with the potential to reduce cardiovascular and systemic side effects, supporting continued development of targeted therapies for inflammatory disorders.
