PABLO PELEGRIN VIVANCOS

Our laboratory study two basic aspects of innate immunity mechanisms:

1. Activation of inflammasome and pro-inflammatory cytokines in response to danger signalsduring the initial phase of inflammation.
Danger signals are endogenous host molecules that are not in place, such signals include the presence of ATP in the extracellular space. Extracellular ATP is recognized by P2X7 receptor activation in macrophages activating the release of mature interleukin (IL)-1 through caspase-1 activation. Caspase-1 activation is dependent on the assembly of an intracellular protein platform termed the inflammasome, which is formed by a NLR receptor that is responsible for detecting such danger signals.
We are studying the involvement of inflammasome activation by extracellular ATP signaling in different diseases, this pathwayis emerging as the responsible for sterile inflammatory conditions, such as rheumatoid arthritis. This concept of danger signals activating the immune system could be the origin of the complex cytokine network that orchestrates the inflammatory response.


2. Mechanisms involved in the resolution of the inflammation.
Alternativeactivated macrophages are critical to the resolution of inflammation. We are interested in the actions of P2X7 receptors on these macrophages and the basic mechanisms by which macrophages switch from pro-inflammatory to anti-inflammatory phenotypes. We study the role of extracellular ATP signaling and metabolism over a dynamic macrophage polarity gradient from pro-inflammatory through anti-inflammatory phenotypes. We find new mechanism to promote inflammatory resolution to chronic inflammatory diseases.