Scientists Uncover New Autoimmune Disease Genes

Rare Daily Staff

Researchers have uncovered new genetic clues behind autoimmune diseases by looking at how DNA folds inside rare immune cells, offering fresh insight into conditions such as Crohn’s disease.

In a study published in Nature Genetics, scientists from the UK’s Medical Research Council Laboratory of Medical Sciences and Imperial College London, working with international collaborators, mapped the three-dimensional structure of DNA in a little-studied group of immune cells known as type 3 innate lymphoid cells (ILC3s). These cells play a key role in protecting tissues like the gut but can also drive inflammation when misregulated.

Although DNA is often depicted as a simple double helix, it is tightly packed and folded inside cells. This folding brings distant stretches of DNA into close contact, allowing regulatory regions—called enhancers—to switch genes on or off. Many genetic variants linked to diseases sit within these enhancer regions, but identifying which genes they influence has been a long-standing challenge.

To tackle this, the team developed a new technique called mini-Capture Hi-C, which can map DNA interactions using far fewer cells than previous methods. This made it possible to study rare cell types like ILC3s for the first time.

Using this approach, the researchers identified more than 100 genes in ILC3s that may be affected by genetic variants associated with Crohn’s disease, a form of inflammatory bowel disease that affects millions of people worldwide. About half of these genes were already known to be involved in the disease, while the rest had not previously been linked to it.

One of the most unexpected findings involved the gene CLN3, which is best known for its role in Batten disease, a rare neurological disorder. The researchers discovered that CLN3 also plays a role in immune function, influencing how strongly ILC3s produce inflammatory signals. Follow-up experiments confirmed this effect, pointing to a previously unrecognized connection between the nervous and immune systems.

The findings help explain how small genetic differences can alter immune cell behavior—potentially increasing or reducing inflammation—and highlight new biological pathways that could be targeted in future treatments.

Beyond Crohn’s disease, the study demonstrates the value of examining the 3D structure of the genome to better understand how genetic risk factors operate. By linking disease-associated DNA variants to the genes they control, researchers can move closer to identifying precise therapeutic targets.

The work also underscores the importance of studying rare cell types, which may hold critical insights into disease mechanisms that are missed in more commonly analyzed cells.