3D genome mapping ties Crohn's disease risk to rare immune cells

A study published in Nature Genetics in August 2026 used a low‑input promoter capture Hi‑C method to map three‑dimensional DNA contacts in human type 3 innate lymphoid cells (ILC3s). The technique, developed by Prof. Valeriya Malysheva, allowed researchers to work with the scarce ILC3 population and connect distant regulatory DNA regions to over 100 candidate genes linked to Crohn's disease risk. The international consortium—including the MRC Laboratory of Medical Sciences (UK), VIB‑UAntwerp Center for Molecular Neurology (Belgium), Cincinnati Children’s Hospital and Imperial College London (US)—identified both known inflammatory‑bowel‑disease genes and novel ones such as CLN3, a gene previously associated with Batten disease. Functional follow‑up showed CLN3 influences inflammatory signaling in ILC3s, highlighting unexpected links between the nervous and immune systems. The findings demonstrate how 3D genome architecture in rare immune cells can clarify the mechanisms by which genetic variants contribute to autoimmune disease.