While the immune system does act as a multi-faceted protective system when dangerous bacteria and viruses come knocking, it is also known to “misbehave.” For not completely understood reasons, occasionally the immune system overreacts, targeting the body’s own, health cells as if they were pathogenic. New research shines a light on the genetic expression of certain variants that could help explain why immune cells go rogue and send unnecessary signals.
The goals from a study done by researchers at the Washington University School of Medicine initially were to observe and understand how both innate lymphoid cells of the non-specific, first-response part of the immune and T helper cells of the adaptive immune system could be sending the same signals to other immune cells during a pathogenic invasion. What they ended up finding, though, was much more than they anticipated.
They found that there are specific gene sequences whose activity is like a “master dimmer switch” for how innate lymphoid cells and T helper cells react during an infection. Like all genes, these sequences of DNA are prone to mutation, and the researchers saw that certain variants of these control genes can cause innate lymphoid cells and T helper cells to overreact, sending signals for backup when none is needed, a process they believe leads to autoimmune diseases like diabetes, rheumatoid arthritis, Crohn’s disease, and ulcerative colitis.
In their study, recently published in the journal Cell,
the researchers looked at cell samples from human tonsils. After analyzing different levels and patterns of gene expression, they were able to isolate a specific group of DNA regions that govern the activity of both innate lymphoid cells and T helper cells. The scientists are calling these DNA regions “super-enhancers.”
Super-enhancers appear to regulate genes in the two immune cells that characterizes everything about them, from how they respond in an emergency situation to how they recruit other cells to an infected site of the body. This is the first time such a group of controlling genes has been identified for innate lymphoid cells and T helper cells.
Now that we know where the master switches are, we can see that those variants are associated with autoimmune disease because they affect the regulation of these immune cells,” said co-senior author of the study Marco Colonna, MD.
The researchers are hopeful that this surprising finding will lead to individualized treatments for people with different kinds of autoimmune diseases that could be related back to a specific super-enhancer.
Sources: Washington University School of Medicine