When the body is under attack from pathogens, the immune system must react quickly to prevent or contain an infection. But how do our defense cells stay ready when no attacker is in sight? Scientists from Vienna have uncovered a surprising explanation: the immune cells are constantly stimulated by healthy tissue, which keeps them active and primed to respond to potential threats.
The key lies in the JAK-STAT signaling pathway, a crucial communication system that links signal detection on the cell surface to the core regulatory machinery of immune cells. This pathway not only activates the immune response during an infection, but also maintains the cells' vigilance when no pathogens are present.
To understand this delicate balance, the research team examined twelve mutant mouse models, each with a genetically altered component of the JAK-STAT pathway. They found that these mice lacked some of the characteristic gene activity and epigenetic regulation associated with the immune cells' standby state. A similar effect was observed when the defense cells were removed from their tissue environment and kept in cell culture, suggesting that the tissue environment plays a crucial role in maintaining the cells' identity and readiness.
By analyzing the gene expression and epigenetics of immune cells and tissue samples, the researchers were able to demonstrate that JAK-STAT signaling has different functions when the immune cells are on standby versus when they are actively responding to pathogens. This insight could pave the way for future medications that selectively enhance the immune system's vigilance, without causing unnecessary damage.
"Our study provides insights into the role of the immune system: not only does it react to attacks, but it also maintains vigilance without causing unnecessary damage," explains Mathias Müller, co-author on the paper published in Nature Immunology. This research has important implications for understanding and potentially treating immune-related diseases and cancer, as the JAK-STAT pathway is sometimes pathologically altered in these conditions.