16.04.2020: New findings by researchers from the Technical University of Denmark Department of Health Technology (DTU Health Tech), in collaboration with researchers from the Unit of Functional Cancer Genomics at University of Veterinary Medicine Vienna, provide new insights regarding future therapies for human immunological diseases. 

Our immune system contains specialized cells that are the first line of defense against pathogens. These cells are called gamma delta T cells and reside mainly in organs like the gut, lung, skin and lymph nodes. These specific T cells can also promote diseases like psoriasis and multiple sclerosis. It is therefore important to understand the basic biology of the gamma delta T cells in order to devise ways to manipulate them and use them therapeutically during infection and inflammation.

The study „The neonatal microenvironment programs innate gamma-delta-T cells through the transcription factor STAT5“ was conducted in the research group “T cell signaling and development” headed by Vasileios Bekiaris, and resulted in two major discoveries:

• STAT5, a molecule that binds and alters DNA structure, is necessary for the growth of certain types of gamma delta T cells during early (neonatal) life. Mice engineered to lack STAT5 do not produce these T cell subtypes and are resistant to a disease that models multiple sclerosis. Expertise in STAT5 mouse models from the team of  Richard Moriggl at the University of Veterinary Medicine Vienna assisted in uncovering the exact molecular details of how STAT5 acts to regulate these T cells.
• A new type of gamma delta T cells was discovered that can be found only in the gut. This new cell type develops during neonatal life, has distinct functions from other types of gamma delta T cells and requires STAT5 for its growth.

These findings can benefit future therapies for human disease in two ways. Firstly, the researchers propose that targeting the molecule STAT5 will suppress gamma delta T cells and therefore inflammatory or malignant diseases associated with these cells. For example, drugs that inhibit STAT5 could be beneficial in conditions like multiple sclerosis or psoriasis, in gamma delta T cell cancers, or perhaps in damping inflammation associated with viruses like SARS-CoV-2.

Secondly, they propose that the new cell type they identified in the gut is a major defense mechanism against intestinal infections shortly after birth. According to WHO and UNICEF, approximately 7,000 babies die every day within the first four weeks of life, with infection ranking as the third most common cause of death. The researchers believe that manipulation of these cells in the neonate may help us to boost immunity in vulnerable neonatal populations. 

* STAT5 produced by gamma delta T cells is important for their growth during early (neonatal) life and, therefore, for their response to infection and inflammation. STAT5 is also important for a new type of gamma delta T cells that is specific to the gut. Inhibition of STAT5 may be useful in treating inflammatory diseases like multiple sclerosis (MS) or psoriasis, whereas manipulation of gamma delta T cells (e.g. functional enhancement) may be useful to prevent infections.