From the NIH National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

• Scientists find a novel mechanism that controls the development of autoimmunity - NIAMS Intramural Research Program Scientific Director John O'Shea, M.D., and colleagues from the Molecular Immunology and Inflammation Branch of the NIH National Institute of Allergy and Infectious Diseases (NIAID) have recently discovered that eliminating a protein called "furin" from immune cells in mice can lead to the development of autoimmune disease. Because of furin's known role in a wide range of diseases, other research teams are exploring the therapeutic potential of furin-blocking drugs. The NIAMS/NIAID discovery suggests that the development of such drug interventions could have the unexpected side effect of increasing the risk of autoimmune disease.

• NIAMS scientists find potential new way to block inflammation in autoimmune disease - Richard Siegel, M.D., Ph.D., and his colleagues in the NIAMS Immunoregulation Group have identified a promising new target for autoimmune disease treatment--a cell surface receptor called DR3. The scientists' findings suggest that blocking this receptor could slow or stop the damaging inflammation characteristic of autoimmune diseases, potentially without leaving the body vulnerable to serious infections, as many current therapies do.

• Molecular pathway in muscle helps explain effectiveness of diabetes interventions - Under the direction of chief Vittorio Sartorelli, M.D., scientists at the NIAMS Laboratory of Muscle Stem Cells and Gene Regulation demonstrated for the first time in a mouse model that skeletal muscle cells cultured in a low-calorie environment are unable to grow into mature muscle cells. The scientists also described for the first time the molecular pathway involving the protein SIRT1 that becomes activated in mouse skeletal muscle cells when they receive fewer calories. Their work shows that SIRT1 is a molecule that allows skeletal muscle to read a low amount of nutrients in the environment and suppress genes that promote cell differentiation, thereby conserving energy.

This research also demonstrates that two interventions that can control diabetes--reduced caloric intake and metformin--both target SIRT1.

• Scientists discover how vitamin A (retinoic acid) can influence inflammatory responses - John O'Shea, M.D., and Arian Laurence, Ph.D., and their colleagues in the NIAMS Molecular Immunology and Inflammation Branch recently discovered how retinoic acid signaling can promote or suppress the activity of helper T cells, a class of immune cells involved in inflammatory responses. Understanding how the newly discovered mechanism regulates the balance between two kinds of helper T cells--pro-inflammatory Th17 cells and anti-inflammatory T regulatory cells--could eventually yield benefits for people with autoimmune disease.
--Source: NIAMS IRPartners, Winter 2008