2024-08-12 カリフォルニア大学サンタバーバラ校(UCSB)
<関連情報>
- https://news.ucsb.edu/2024/021575/appetizer-can-stimulate-immune-cells-appetite-boon-cancer-treatments
- https://www.sciencedirect.com/science/article/pii/S153458072400457X
事前のFc受容体活性化により、マクロファージは長期的・短期的メカニズムでIgGに対する感受性を高める Prior Fc receptor activation primes macrophages for increased sensitivity to IgG via long-term and short-term mechanisms
Annalise Bond, Sareen Fiaz, Kirstin Rollins, Jazz Elaiza Q. Nario, Erika T. Snyder, Dixon J. Atkins, Samuel J. Rosen, Alyssa Granados, Siddharth S. Dey, Maxwell Z. Wilson, Meghan A. Morrissey
Developmental Cell Published: August 12, 2024
DOI:https://doi.org/10.1016/j.devcel.2024.07.017
Graphical abstract
Highlights
- Oligomerization of FcR-ITAM domains is sufficient to trigger phagocytosis
- Prior subthreshold activation of FcRs enhances antibody-dependent phagocytosis
- FcR activation increases FcR mobility within 1 h
- FcR activation increases phagocytosis for days by changing gene expression via Erk
Summary
Macrophages measure the “eat-me” signal immunoglobulin G (IgG) to identify targets for phagocytosis. We tested whether prior encounters with IgG influence macrophage appetite. IgG is recognized by the Fc receptor. To temporally control Fc receptor activation, we engineered an Fc receptor that is activated by the light-induced oligomerization of Cry2, triggering phagocytosis. Using this tool, we demonstrate that subthreshold Fc receptor activation primes mouse bone-marrow-derived macrophages to be more sensitive to IgG in future encounters. Macrophages that have previously experienced subthreshold Fc receptor activation eat more IgG-bound human cancer cells. Increased phagocytosis occurs by two discrete mechanisms—a short- and long-term priming. Long-term priming requires new protein synthesis and Erk activity. Short-term priming does not require new protein synthesis and correlates with an increase in Fc receptor mobility. Our work demonstrates that IgG primes macrophages for increased phagocytosis, suggesting that therapeutic antibodies may become more effective after initial priming doses.
