A naukri.com initiative
Bioengineer
1w
29
Image Credit: Bioengineer
Tracing Immune Restraint Through Time: Uncovering the PD-1 Pathway Origins in Sharks
- Researchers have discovered that the PD-1 immune checkpoint molecule is highly conserved across various jawed vertebrates, from sharks to humans, reshaping our understanding of immune system evolution and offering potential for future immunotherapies.
- The study provides molecular insights into PD-1, its ligands PD-L1 and PD-L2, and associated phosphatases, revealing conserved features maintained over millions of years.
- PD-1's role in regulating immune responses and its significance in cancer immunotherapy have been well-established, with recent findings challenging the belief that PD-1 existed only in tetrapods.
- Through comparative genomic and molecular evolutionary analysis, the research traces the PD-1 gene and its partners, highlighting conserved structural features and interaction interfaces.
- Distinct characteristics of PD-L2 from PD-L1, particularly in the immunoglobulin constant domain, point to potential specialized roles evolved after ancestral fish lineages.
- The study reveals evolutionary conservation in intracellular signaling motifs of PD-1 and introduces SHP-2L, an ancient phosphatase variant lost in rodents and higher primates, adding complexity to PD-1 signaling.
- Expression analyses show PD-1 enrichment on regulatory T cells in fish, supporting its enduring role in immune regulation across vertebrates for hundreds of millions of years.
- Understanding the evolutionary conservation of the PD-1 axis could lead to improved immunotherapies by leveraging ancestral features and exploring the broader vertebrate immune system.
- The research underscores the importance of immune checkpoints in maintaining immune balance and highlights the evolutionary imperative of immune restraint.
- The study in Frontiers in Immunology reflects a collaborative effort among Japanese scientists to uncover fundamental biological questions with translational relevance.
- These findings redefine the PD-1 system as a universal sentinel in maintaining immune equilibrium across jawed vertebrates, offering insights for future therapeutic approaches rooted in evolutionary biology.
Read Full Article
1 Like
For uninterrupted reading, download the app