Type 1 interferons, among the first of many cell communication mediators now called cytokines, were discovered some 50 years ago. Scientists at the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) and Brown University have found a new way that they help the body fight infection and regulate immune responses.
John O'Shea, M.D., of NIAMS' Molecular Immunology and Inflammation Branch, along with his NIAMS and Brown University colleagues, have found that the Type 1 interferons IFN-a and IFN-b—already well-known for their direct therapeutic effects against virus infections—also stimulate production of the infection-fighting type 2 interferon, IFN-g. To accomplish this, say the investigators, IFN-a and IFN-bactivate an intermediary signaling protein called STAT4, which binds the IFN-g proximal promoter and is needed to produce the Type 2 interferon. The work, done in a mouse model of viral infection, shows that Type 1 IFN and STAT4 are critical for IFN-g production, which is critical for host response against pathogens.
This insight into a new pathway for cytokine regulation through cellular signaling might eventually help scientists manipulate cytokine activity to therapeutic advantage.
"Even though the Type 1 interferons have been the most widely used cytokines clinically, there has been much about them that we haven't understood," said Dr. O'Shea."We're excited about the new trick that these 'old dog' cytokines have taught us!"
Nguyen K, Watford W, Salomon R, Hofmann S, Pien G, Morinobu A, Gadina M, O'Shea J, Biron C. Critical role for STAT4 activation by Type 1 interferon in the interferon-g response to viral infection. Science 2002; 297:2063-2066.