IL-10 constrains sphingolipid metabolism to limit inflammation. (https://pubmed.ncbi.nlm.nih.gov/38383790/)

These scientists wanted to understand how a molecule called interleukin-10 (IL-10) helps to reduce inflammation in our bodies. They found that when IL-10 is missing, it can lead to a serious condition called inflammatory bowel disease. However, they were not sure exactly how IL-10 works to calm down inflammation.

To study this, the scientists looked at another type of molecule called very long chain ceramides, which are found in our cells. They discovered that when IL-10 is not present, there is an increase in a specific type of ceramide called saturated very long chain ceramides. These ceramides can make inflammation worse.

The scientists then did an experiment where they removed the gene responsible for making these saturated ceramides. They found that this reduced the inflammation seen in cells lacking IL-10, both in the lab and in living organisms.

They also found that the increase in saturated ceramides was linked to a decrease in the production of another type of fat in the cells. By restoring this fat, they were able to reduce the production of the harmful ceramides and inflammation.

Their study showed that the persistent inflammation caused by these ceramides depended on the activity of a specific protein called REL. By understanding this process, the scientists suggested that correcting the balance of these fats in our cells could be an important way to treat inflammation when IL-10 is not working properly.

York AG., Skadow MH., Oh J., Qu R., Zhou QD., Hsieh WY., Mowel WK., Brewer JR., Kaffe E., Williams KJ., Kluger Y., Smale ST., Crawford JM., Bensinger SJ., Flavell RA. IL-10 constrains sphingolipid metabolism to limit inflammation. Nature. 2024 Feb 21. doi: 10.1038/s41586-024-07098-5.