A guide to complement biology, pathology and therapeutic opportunity

Area of Science:

• Immunology
• Molecular Biology
• Developmental Biology

Background:

• The complement system is traditionally viewed as a key innate immune effector mediating host defense and tissue homeostasis.
• Emerging evidence reveals complement's broader involvement in fundamental biological processes beyond innate immunity.
• Complement engages in complex crosstalk with various signaling pathways, both extracellularly and intracellularly.

Purpose of the Study:

• To provide a comprehensive overview of the system-wide functions of complement.
• To highlight paradigm shifts in understanding complement pathobiology.
• To discuss the role of complement in evolution, neurodevelopment, tissue regeneration, and cancer immunity.

Main Methods:

• Review of current scientific literature.
• Synthesis of evidence from diverse fields including immunology, developmental biology, and cancer research.
• Analysis of clinical developments in complement therapeutics.

Main Results:

• Complement's functions extend to guiding developmental processes and cell trajectories.
• Crosstalk with other pathways shapes tissue immunometabolism and regeneration.
• Dysregulated complement activation contributes to inflammatory tissue pathology.
• New therapeutic strategies targeting complement are emerging.

Conclusions:

• Complement is a multifaceted system with critical roles in immunity, development, and regeneration.
• Understanding complement's expanded functions offers new therapeutic avenues.
• Targeting complement pathways holds promise for treating various diseases.