Scientists at the National Institutes of Health (NIH) have found a mechanism in the immune systems of mice that can lead to the development of autoimmune disease when turned off. The findings shed light on the processes that lead to the development of autoimmunity and could also have implications for the development of drugs to increase the immune response in diseases such as cancer and HIV.
The scientists from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) and the National Institute of Allergy and Infectious Diseases (NIAID), both part of the NIH, studied immune system T cells — specifically the helper T cell, an immune system component that helps other cells fight infection. They focused on the protein furin, an enzyme that plays an important role in the functioning of T cells.
Scientists have been limited in their ability to study the protein furin, because other enzymes can perform some of the same functions. Also, furin is essential to life, so scientists have been unable to create a mouse without furin that lives past the embryo stage of development. Since the NIH scientists were unable to see what a mouse without furin would look like, they collaborated with Belgium scientists to create a mouse without furin only in T cells. What they discovered was that mice without furin in these cells developed systemic autoimmune disease. This means that the immune systems of the mice attacked their own cells and tissues throughout their bodies.
The researchers found that deleting furin in helper T cells affected the functioning of two types of T cells, regulatory and effector T cells. The former cells, also called Tregs, promote immune tolerance to the body’s own cells and tissues. Upon further examination, the researchers found that mice lacking furin in Tregs had lower levels of a specific protein, TGF-ß1, which is produced by these cells and is important for their ability to preserve immune tolerance. However, the researchers noted that effector T cells also produce TGF-ß1. They found 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.
Release date: August 13, 2008
Source: NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases