Regulation of inflammatory Th17 cells in autism spectrum disorder
Dan Littman, M.D., Ph.D.
New York University School of Medicine
Numerous studies suggest that abnormal activation of the immune system plays a role in causing autism. Some behavioral problems in children have been traced back to viral infections in their mothers during pregnancy. Studies in experimental mice have shown that revving up the mother’s immune system during pregnancy results in offspring with altered gene expression in the brain and problems with behavioral development. More specifically, immune system changes and autoimmune disorders, such as inflammatory bowel disease, have been found in individuals with autism.
Dan Littman and his colleagues at New York University School of Medicine suspect that the link between immune function and autism lies in a newly discovered subset of immune cells called Th17 cells.
Th17 cells are so named because they produce the inflammation-inducing signaling molecule interleukin-17. Their normal role is thought to be in fighting bacterial and fungal infections, but if this defense mechanism goes awry, Th17 cells can cause inflammatory tissue damage that eventually leads to rheumatoid arthritis, multiple sclerosis, Crohn’s disease, psoriasis and other autoimmune and inflammatory diseases.
Littman and colleagues propose to study the contribution of these cells to autism using both mouse models and clinical samples. The researchers plan is to use experimental mice lacking Th17 cells to shed light on the cells’ role in the behavioral changes linked to activation of the maternal immune system. The researchers also plan to examine the function of Th17 cells in mice lacking MeCP2, the gene that is defective in the autism-related Rett syndrome.
Clinically, the researchers plan to compare levels of Th17 cells and the chemical signals they produce in blood samples from individuals with autism and healthy controls. They will also look at the distribution of other immune cells that can mediate inflammation. The findings from their study may strengthen understanding of the connection between autism and the immune system.