Discovery: Uncommon Genetic Mutation Provides Insights into Type 1 Diabetes Prevention

UK researchers at the University of Exeter have identified an unprecedented genetic mutation present in two siblings, unseen in any other individuals. This finding opens avenues for novel treatment strategies in the realm of type 1 diabetes.

The mutation occurs within the gene responsible for encoding programmed death-ligand 1 (PD-L1) protein. A recent study elucidates how this mutation potentially triggers the autoimmune manifestation of diabetes observed in affected children from a very early age.

Matthew Johnson, a molecular geneticist from the University of Exeter in the UK, explains, “We scoured various large-scale datasets worldwide but haven’t encountered another family with similar genetic characteristics. Hence, these siblings offer a unique and profoundly significant opportunity to probe the consequences of PD-L1 gene disruption in humans.”

Type 1 diabetes, also referred to as autoimmune diabetes, arises due to the immune system’s erroneous attack on pancreatic beta cells, halting the normal production of insulin. Individuals afflicted with this condition must administer insulin injections regularly to regulate their blood sugar levels.

The siblings, aged 10 and 11 during the study, developed diabetes within the initial weeks of their lives. Subsequent examination of immune cells from the siblings corroborated that their distinctive genetic mutation impeded the proper functioning of the PD-L1 protein.

Role of PD-L1 and PD-L2 in Immune System Regulation

Given that PD-L1 and its PD-1 receptor collaborate as a regulatory mechanism to restrain the immune system, and considering that therapies targeting PD-L1 in cancer treatment can precipitate the onset of diabetes, the role of PD-L1 appears pivotal in preventing the onset of type 1 diabetes.

However, in an unexpected turn, the immune systems of the two siblings appeared to function relatively normally, even in the absence of the immune system regulation typically provided by PD-L1 and PD-1.

Physician-scientist Masato Ogishi from Rockefeller University in New York suggests, “We hypothesize that PD-L2, although less studied compared to PD-L1, might act as a backup system in the absence of PD-L1.”

Implications and Future Directions

A significant inference drawn by the researchers is that while the PD-L1 protein plays a critical role in averting type 1 diabetes, it is not indispensable for maintaining many other immune system functions at their usual levels.

Insights gleaned from the genetic mutation, alongside the association between cancer treatment and diabetes, hold promise for discovering novel approaches to address the onset of type 1 diabetes. Understanding how PD-L1 prevents diabetes and how PD-L2 functions as a backup could be pivotal.

“We need to elucidate the intercellular communication crucial for preventing autoimmune diabetes,” remarks immunologist Timothy Tree from King’s College London in the UK.

“This discovery enhances our understanding of the development of autoimmune diabetes types like type 1 diabetes. It introduces a potential new target for treatments that could forestall diabetes in the future.”

Read the original article on: Science Alert

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