To discuss the roles of calcitonin gene-related peptide (CGRP) in immunity, inflammation, infection, autoimmunity, and cancer.
Approach:
CGRP Signaling: CGRP mediates its effects through a heterodimeric G-protein-coupled receptor complex involving CLR and RAMP1.
Context-Dependent Roles: CGRP exhibits both anti-inflammatory and pro-inflammatory effects depending on the immune context, influencing various immune cell types such as macrophages and T cells.
Key Findings:
CGRP primarily exerts anti-inflammatory effects on innate immune cells but can promote pro-inflammatory signaling in certain conditions.
In adaptive immunity, CGRP generally suppresses Th1 responses but can enhance Th1 differentiation during acute viral infections.
CGRP depletion in severe infections like sepsis impairs neuro-immune protection.
Tumors can exploit CGRP signaling to suppress anti-tumor immunity and promote cancer cell growth.
Interpretation:
CGRP has context-dependent roles in the immune system that can either restrain or promote inflammation.
Limitations:
Most mechanistic insights are derived from murine models and in vitro studies, limiting direct applicability to human conditions.
The complexity of CGRP's roles necessitates careful targeting to avoid disrupting physiological homeostasis.
Conclusion:
The review discusses the potential of anti-CGRP monoclonal antibodies for conditions associated with dysregulated CGRP signaling.
