Some autoimmune diseases, like lupus, affect multiple tissues, but some, like inflammatory bowel disease, affect only specific types. A new study reveals that HDAC7 controls tissue-specific autoimmunity in othertissues via its action in the thymus, a mechanism which you might not suspect. (Well, unless you searched GeneCentrix’s target tool with HDAC7, and saw that the thymus was glaringly at the top of your search results! Watch a demo here for more information.)
HDAC7 was previously known by GWAS studies to be associated with two gut autoimmune diseases: inflammatory bowel disease (IBD; Crohn’s disease and ulcerative colitis) and primary sclerosing cholangitis (PSC). However, it was not understood how HDAC7 played into those diseases. These authors found that loss of HDAC7 resulting in key immune cells, called natural killer (NK) cells, to be defective in various functions during their maturation/programming in the thymus. As it turns out, these NK cells home to the gut and play a large role in the balance of inflammation and anergy in those tissues. So that is how a defect in the thymus results in a disease far away in the gut.
The authors demonstrated this by deleting HDAC7 in mice and reconstituting their immune systems with properly programmed NK cells. THe HDAC7 deficient mice developed symptoms and pathology similar to IBD and PSC, which were resolved upon reconstitution with normal NK cells.
Tissue-specific phenotypes can be confusing, but can also provide profitable clues to mechanism and function in vivo. Genecentrix is a big believer in analyzing tissue specificity alongside genetics and pharmacology to solve drug discovery mysteries.