Scientists from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the NIAID have turning off the production of the protein furin in helper T cells can lead to the development of autoimmune diseases.
Because this protein is essential to life, scientists thus far have been unable to create a mouse without furin that lives past the embryo stage of development. The NIH scientists thus collaborated with Belgium investigators to create a mouse without furin only in helper T cells.
“Inhibiting furin has been thought to reduce growth of malignant cells or to block infections by preventing essential activation of a pathogen,” notes John J. O'Shea, M.D., chief of the NIAMS' Molecular Immunology and Inflammation Branch. “However, these results suggest that the development of drug interventions could have an unexpected side effect of increasing the risk of developing autoimmune disease.”
The researchers found that deleting furin in helper T cells affected the functioning of two types of T cells, regulatory and effector T cells. Upon further examination, the researchers noticed that mice lacking furin in regulatory T cells had lower levels of the protein TGF-ß1. They noted, however, that effector T cells also produce TGF-ß1. They discovered that furin is also needed for TGF-ß1 production by effector T cells and that the absence of furin in effectors makes these cells more aggressive in causing autoimmune disease and tissue damage.
The study paper appears in this week’s edition of Nature.