A pathway responsible for inflammatory responses is hyperactive in dendritic cells of people with IBD. Credit: KATERYNA KON/ SPL/ GETTY IMAGES
An active signalling pathway worsens inflammation in mice with colitis by reducing the production of retinoic acid from vitamin A, which is important for immune system balance1. The finding can help develop treatments for inflammatory bowel disease (IBD).
Scientists at the National Institute of Immunology in Delhi discovered that non-canonical NF-kappa B pathway signalling, a pivotal pathway that brings about inflammatory responses, is elevated in the immune cells (dendritic cells) of people with IBD.
The researchers investigated the link between this heightened activity and disease in a mouse model. They used biochemical assays and RNA sequencing to examine cells from the guts of mice with chemically induced colitis. They also worked with mice that specifically lacked the signalling in their immune cells to see how this affected colitis development.
The communication route disrupts the enzyme retinaldehyde dehydrogenase 2 (Raldh2), which converts vitamin A to retinoic acid, a biologically active metabolite.
“This enzyme downregulation leads to imbalance of the gut microbiota and immune response. So immune cells are not able to communicate the ongoing inflammation,” says co-author Alvina Deka.
If inflammation persists, it leads to a chronic state, which is a common cause of IBD. By turning off the pathway in immune cells, the inflammation in the mice's guts got better. According to co-author Naveen Kumar, the pathway could be a target for treating similar diseases in humans.
