The human IL-7 receptor gene: Deletions, polymorphisms and mutations

Most T cell subsets depend on IL-7 for survival. IL-7 binds to IL-7Rα and γc, initiating the signaling cascade. Deletion of IL-7Ra in humans has, for some time, been known to cause severe combined immunodeficiency. More recently, polymorphisms in IL-7R have been shown be a risk factor for a number of diseases that are autoimmune or involve excess immune and inflammatory responses including multiple sclerosis, type 1 diabetes, rheumatoid arthritis, primary biliary cirrhosis, inflammatory bowel disease, atopic dermatitis, inhalation allergy, sarcoidosis and graft-versus host disease. The polymorphism that affects risk to most of these immunopathologies is T244I at the border of the extracellular domain and the transmembrane region. The same region has recently been shown to harbor gain-of-function mutations in acute lymphoblastic leukemia. These studies have suggested new therapies that target the IL-7 pathway.

► Polymorphisms in IL-7R have recently been linked to a number of immunopathologies. ► Immunopathologies include multiple sclerosis, type 1 diabetes and rheumatoid arthritis. ► They also include inflammatory bowel disease, inhalation allergy and others. ► We propose a new mechanism for the IL-7R polymorphism effect in immunopathology. ► Gain-of-function mutations in IL-7R occur in acute lymphoblastic leukemia.