Francisco Quintana, PhD

A research team led by Francisco Quintana, PhD, BWH Department of Neurology, has identified interleukin-21 as an inducer of interleukin-22 production in CD4+ T immune cells. Interleukins are cell-signaling molecules that play a role in white and red blood cell development and immune system regulation.

Interleukin-22, which is made by innate lymphoid cells and CD4+ T immune cells, is important in defending against pathogens entering the body, particularly through the mucosal surfaces in the gut. The researchers sought to learn more about how interleukin-22 production is regulated in CD4+ T immune cells.

They found that CD4+ T cells produce interleukin -22, but not other molecules such as interleukin-17, when triggered by interleukin-21. The process involves interleukin-21 activating the STAT3 protein, which controls the activity of the promoter of the interleukin-22 gene. Particularly, STAT3 controls how the promoter interacts with the aryl hydrocarbon receptor, a protein that regulates gene transcription in response to environmental and metabolic cues.

Finally, the researchers also discovered that this pathway controls the development of intestinal inflammation in mice.

“These findings shed new light on the mechanisms through which the environment modulates the immune response via the aryl hydrocarbon receptor, and might guide new therapeutic avenues to control pathogenic inflammation,” said Quintana.

The study was published online May 6, 2014 in Nature Communications.