ucsdhealthsciences: JUST THE FAQs: Why Do Macrophages Do What They Do? A new study led by Christophe

ucsdhealthsciences: JUST THE FAQs: Why Do Macrophages Do What They Do? A new study led by Christopher K. Glass, MD, PhD, UC San Diego School of Medicine professor, answers longstanding questions about what makes a macrophage the sort of macrophage it is. What are macrophages and what do they do? Macrophages are a type of immune cell. They respond to infections and injuries in the human body. Macrophages are found in all tissues of the body, where they are best known for engulfing invading pathogens and cleaning up damaged tissue. But on top of that, macrophages also take on specialized roles that serve the needs of their own home tissues. For example, macrophages in the brain (called microglia) remove toxic protein aggregates and develop the ability to “prune” extra connections between neurons. Meanwhile, macrophages in the peritoneum, the body cavity surrounding the large and small intestines, secrete factors that control the functions of other immune cells. How do tissue macrophages attain their specialized functions? Before this study, not much was known about how macrophages in each tissue attain their specialized functions. It also wasn’t well understood how some macrophages turn on one set of genes while others use different genes to perform their specialized duties. But now Glass and his team have made two important discoveries. The first is that the peritoneum and the brain send out different “instructions” (soluble factors) that tell their local macrophage populations where they are and what they should do. And these instructions are constantly required to maintain the distinct “personalities” of microglia and peritoneal macrophages. If the macrophages are removed from their normal environments and placed into culture, they lose many of the distinguishing features they normally have in living systems. The second major discovery has to do with macrophage gene regulation. The turning off and on of genes is controlled by special regions of the genome called enhancers. These are short DNA segments that don’t code for proteins but instead have the potential to activate nearby genes. This study provides insights into how different tissue environments (such as in the brain vs. the peritoneum) direct specific patterns of gene expression via enhancers. What could this study mean for human health? Most human genetic variation associated with disease is in regions of the genome that don’t code for proteins. This study indicates how non-coding mutations could affect enhancers that are required for the specific functions of macrophages and microglia in common human diseases, such as diabetes and neurodegenerative diseases. These findings provide important general insights into understanding how such genetic variation can affect disease risk in humans. To learn more read the paper, published Dec. 4 by Cell. Pictured: A scanning electron micrograph of a false-colored macrophage digesting a bit of debris. Image courtesy of Steve Gschmeissner. -- source link
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