Multiscale 3D genome organization underlies ILC2 ontogenesis and allergic airway inflammation

Michieletto MF, Tello-Cajiao JJ, Mowel WK, Chandra A, Yoon S, Joannas L, Clark ML, Jimenez MT, Wright JM, Lundgren P, Williams A, Thaiss CA, Vahedi G, Henao-Mejia J. Nat Immunol. 2022 Sep 1. doi: 10.1038/s41590-022-01295-y. Online ahead of print.


Asthma, hay fever and other kinds of allergic airway inflammation depend to a great extent on the activity of airway-resident immune cells called ILC2s. A team led by Jorge Henao-Mejia, MD, PhD, and Golnaz Vahedi, PhD, associate professors of Pathology and Laboratory Medicine and Genetics, respectively, has shown how a precise 3D configuration of ILC2s' DNA is a major factor in this inflammation. The researchers found that the DNA configuration brings a gene needed for ILC2 development and the maintenance of its cellular "identity" into close proximity with transcription factor proteins that keep the gene switched on. They showed that separating the gene from its transcription factors by disrupting this DNA configuration causes the ILC2 population to plummet—and brings a drastic decrease in signs of allergic airway inflammation in a mouse model. Studying the way DNA is folded and organized in cells such as ILC2 should advance the understanding of inflammatory and autoimmune diseases.