CD39 is an enzyme found on the surface of many cells throughout the body. It regulates fundamental biological processes, influencing how cells communicate and respond to their environment. Understanding CD39 provides insight into how the body maintains balance and responds to challenges.
What is CD39
CD39 is formally known as ectonucleoside triphosphate diphosphohydrolase-1 (ENTPD1), also called NTPDase1. This enzyme resides on the outer membrane of cells. Its primary function involves breaking down specific energy-carrying molecules found outside cells, namely adenosine triphosphate (ATP) and adenosine diphosphate (ADP).
CD39 acts on these molecules by removing phosphate groups, converting them into adenosine monophosphate (AMP). This conversion represents the initial step in a cascade that alters the cellular environment. CD39 activity directly influences the availability of these energy molecules, affecting various cellular communication pathways.
How CD39 Influences the Immune System
The AMP produced by CD39 is a precursor for another important molecule. Another enzyme, CD73, converts this AMP into adenosine. Adenosine acts as a signaling molecule, interacting with receptors on cell surfaces to transmit messages. This sequential enzymatic action creates an “adenosinergic axis.”
Adenosine influences immune responses, generally promoting immune tolerance and dampening excessive inflammation. It does this by signaling through receptors that suppress immune cell activity. For instance, adenosine impacts regulatory T cells (Tregs).
Tregs are specialized immune cells responsible for maintaining immune system balance and preventing autoimmunity. By promoting Treg function and expansion, CD39 activity contributes to immune suppression.
This prevents the immune system from overreacting or attacking healthy tissues, maintaining overall immune homeostasis.
CD39 in Disease Development
CD39’s regulatory role in the immune system means altered activity can contribute to disease progression. In cancer, for example, high CD39 activity within the tumor microenvironment is a factor. Tumors exploit this enzyme to create an immunosuppressive shield.
By generating abundant adenosine, tumors inactivate surrounding immune cells that would otherwise attack them. This helps cancer cells evade detection and destruction, allowing tumors to grow and spread. The elevated presence of CD39 on tumor cells and certain immune cells within the tumor contributes to this protective barrier.
Beyond cancer, CD39 also plays a part in conditions like chronic inflammation. Its activity can influence the duration and intensity of inflammatory responses. Similarly, in ischemia-reperfusion injury, which occurs when blood flow returns to tissues after deprivation, CD39’s role in adenosine production can modulate the extent of tissue damage and subsequent inflammation.
CD39 as a Therapeutic Target
Given its impact on immune regulation and disease progression, CD39 has emerged as a promising target for new medical treatments. Modulating its activity offers a strategy to intervene in various pathological conditions.
In cancer, for instance, inhibiting CD39 activity aims to dismantle the tumor’s immunosuppressive shield. This approach allows immune cells to more effectively recognize and eliminate cancer cells. Researchers are exploring methods to achieve this, including developing small molecule inhibitors and specific antibodies that block CD39’s function. Conversely, in certain inflammatory or ischemic conditions, enhancing CD39 activity might be beneficial by promoting adenosine-mediated anti-inflammatory effects and tissue protection.