CCR scientists tease out mechanisms of immune cell communication

Cytokines broadcast messages which stimulate an immune response, but when they are surrounded by dense crowds of cytokine-absorbing cells (as in the image foreground), their messages don’t travel very far. In contrast, tissue regions with few cytokine-absorbing cells (image background) allow messages to travel much farther.

Credit: Altan-Bonnet

When a pathogen enters the body, white blood cells called effector T cells (Teff) produce tiny proteins called cytokines that broadcast the nature and severity of the attack to the rest of the body so that other immune cells can mount an appropriate defense. But the processes that control the reach of cytokine communications remain a mystery.

Now, researchers from the Cancer and Inflammation Program at the Center for Cancer Research and the Ben-Gurion University of the Negev in Israel have discovered that the simple processes of molecular diffusion and absorption control the spread of cytokines through dense body tissues. The simple control mechanisms enable the immune response to tailor itself to the nature and severity of a pathogenic attack and to prevent dangerous autoimmune reactions.

In the study, published April 4 in Immunity, the researchers used mathematical modeling and in vivo experiments to demonstrate that as cytokines diffuse through tissues, they also encounter and bind to receptors on cells, which limit the distance over which they may communicate. For example, in tissues that contain high numbers of a type of white blood cell called regulatory T cells (Tregs), cytokines are quickly absorbed and therefore don’t travel far from their source. Conversely, regions with low Treg densities allow cytokines to spread their message much farther. Although it is still unclear what controls the concentrations of Tregs and other cells that bind cytokines, the findings demonstrate that cytokine messaging can be precisely controlled.

“Now that we understand immune cell communications quantitatively, we can attempt to turn them on and off at will,” said Grégoire Altan-Bonnet, a CCR investigator and a lead author on the study. “Our long-term goal is better immunotherapies through the fine tuning of cell communications.”

Summary Posted: 04/2017