Communication has always been a key characteristic of our society, and it is one of the underlining features of our success. Evolution has allowed us to acquire the ability to speak and but also to develop other types of communications. Verbal, non-verbal, written and visual are a few examples. However, our ability to send information goes far beyond what our eyes can see.

Created with Biorender

 

Just like we are able to use communication to alert those around us of any possible danger, our internal fighters have to be able to do the same. Imagine the number of microorganisms we are being exposed to every single day. Being able to inform nearby cells of possible threats is crucial. Therefore, in order to properly function, our immune system needs to have an exceptional ability to communicate.

But how does this communication actually work? What happens if a cell wants to tell X to a group of cells, and Y to another group of cells? In our language we can say pretty much anything using a combination of words, but what about cells? How does such a complex level of communication happen at a molecular level? … Hold on to your seat, and let’s talk about how cells talk!

 

Cytokines: the words of our molecular language

In order to communicate, our cells have evolved a very cool mechanism which includes a signalling molecule and a receptor. The transfer of information occurs when the signalling molecule binds to the receptor, which ultimately modifies the cell receiving the signal.

These signalling molecules are called cytokines, and they can be released by many different cells in our body (not just immune cells). Most cytokines are soluble factors meaning that they are released from the cell, but some can stay bound to the cellular membrane. Cytokines will act on receptors, which are expressed by a vast number of cell types. Together this means that almost all cells in our body are able to send and receive information using this mechanism.

The word cytokine can bring fear to many people since there are not just one, two or three different cytokines, but many different FAMILIES of cytokines. Each family has different members, each member is released by different cell types (which depends on the situation), and the combination of many different cytokine actions is what leads to the desired cellular result. Breath… I know, it sounds very complicated. But trust me, the idea behind it is very straightforward: sending information to the correct cell, at the correct time, to lead to specific changes!

By now you can already appreciate that the beauty of the immune system is not the act of a single cell (or cell type), but the regulated network of events, that together help us stay healthy. And many times, this regulation is dictated by cytokines!

 

The transfer of information

Imagine that cell X has been placed in a situation of stress. Instead of freaking out, this cell needs to alert the other cells around it. One way to achieve this is by producing cytokines. Cell X will produce and release a high number of cytokine molecules in its surrounding. A signal will occur if this molecule happens to find a receptor. But note, that the binding of the cytokine to the receptor is very specific, meaning that each type of cytokine has its unique receptor.

Cell x (in purple, left) releasing two different types of cytokines in the environment. Cell y (in blue, middle) expressing the receptor specific to the red (circular) cytokine. Cells in gray (right) do not express the specific cytokine receptor and therefore won’t receive the “information” sent by cell x. Created with BioRender

In our scenario, cell Y happens to express the specific cytokine receptor. Note that you should not picture the receptor as an “arm” that will go search for the cytokine. The receptor stays at the surface, and due to the high number of cytokine molecules in the environment, there is a high chance of a cytokine landing on the receptor. This binding allows for the information to translate into changes inside the receiving cell.

The cytokine-receptor interaction leads to the activation of what is called a “signalling cascade”. Yes, a cascade (but more like a tiny, tiny, molecular cascade) is exactly what happens after the initial binding. Picture this. Inside of the receiver cell, there are many proteins present in an “inactive” state. As soon as the cytokine-receptor biding occurs, they will change into the “active” state, one after the other. Meaning that the initial signal will activate protein 1, which will then acquire the ability to activate protein 2, which… you guess.. acquire the ability to activate proteins 3, and so on…

 

So… what’s at the end?

Well, many different things can happen “at the end” of this molecular cascade, but an underlying feature is the ability to generate new proteins.

In our scenario, prior to the signal, cell Y was just chilling. It did not require proteins to take care of any danger. So, this cell didn’t express such proteins. However, cell Y still has the ability to generate a wide range of proteins thanks to its internal “manual” known as the DNA. DNA holds the information necessary to produce proteins, and a cell can access this information when in need.

So, “at the end” of a signalling cascade, cells can activate a type of protein called transcription factors. Ok, I have to admit that many things in science make me happy, but transcription factors hold a very high place on my “happy list”!

Transcription factors are proteins that can bind to our DNA and turn on (or off) the production of a specific protein. Some transcriptor factors are just like “master regulators” which are able to turn on the production of a set of proteins. It sounds like the perfect idea if you want your cell to go from “chilling” to “fighting”. Turning on the “fighting” set of genes (that will make proteins) by activating the correct transcription factors, and your cell is ready to go! Isn’t that just awesome?

Following the binding of the cytokine to its receptor, a signalling cascade will occur. A high number of different proteins will get activated in this process. Many times, at the end of the cascade, there will be the activation of a transcription factor that can turn on the production of new proteins. Created with BioRender.

 

More than just a danger signal

It is important to note that cytokines are much more than signalling molecules following danger. Cytokines are crucial to many aspects of cell biology. The wide range of different responses occurs due to the high number of cytokine types, but also by the combination of cytokine signals that one cell can receive.

Moreover, different cells can express different types of receptors at different time points. This dynamic regulation of receptor expression is essential to allow cells to respond, or not, to environmental cues. All these variables together, allow for a wide range of “communication” to occur.

 

Can it go wrong?

Now you know that cytokines play a crucial role to ensure we stay healthy, but just like everything else… too much of a good thing can be bad. Many different diseases actually result from an inappropriate release of such molecules. Either due to the inappropriate release of cytokine amount or cytokine type.

Sepsis is a classical example of communication going very wrong. This is an extremely dangerous condition that occurs following the overactivation of our immune system. After injury or infection, cytokines are released to ensure the danger is contained. However, during sepsis, there is a massive release of cytokines, a phenomenon known as cytokine storm.

Instead of helping us, this high level of information over activates many immune cells, which then start to attack our own body. Unfortunately, this bad communication can lead to organ failure and even death. What was supposed to be an easy task, the removal of the infection or the repairing tissue, can be become life-threatening due to an unregulated release of cytokines.

 

Harnessing the power of cytokines

At the right dose, however, cytokines are extremely beneficial to us. Therefore, scientists have been exploiting their power to treat different diseases. Cytokine treatments are used to help patients suffering from autoimmune diseases and even cancer.

As I mentioned before, autoimmune diseases occur when our immune cells wrongly attack our own healthy cells. These immune cells that were supposed to be “chilling” are now fighting, which can have very detrimental effects. Therefore, by giving an appropriate cytokine that provides the “hey stop attacking, everything is ok” information, we can help patients with autoimmune diseases. Now you see how crucial it is for us to further understand the role cytokines in each situation.

Cytokine action is one amazing example of how cells are able to talk! I have to admit that I do talk a lot most of the time, but I am 100% sure my cells talk way more than I do… and… I might be using this excuse in the near future. See you next week!

From your immunologist – in training,

Stefanie Valbon