Stanford Report, April 11, 2007

Quick study: microRNA 'dials up' immune response

THE QUESTION: One of the main weapons of the body's immune system is the T cell. These cells must determine when to attack foreign invaders, but they must also recognize when an entity is part of itself, and to suppress its attack. How do T cells learn to develop immunity that is tolerant to "self" but sensitive to that which is foreign?

THE STUDY: The researchers set out to investigate what role a specific microRNA played in the T cell's task of responding to triggers from the outside world. A microRNA is a snippet of RNA that can control protein production through a process similar to RNA interference, the finding that earned a Nobel prize last year for Andrew Fire, PhD, professor of pathology and of genetics. The current study found that a microRNA called miR-181a was able to boost the response and sensitivity of T cells through a chain of biochemical events. Increasing the amount of miR-181a increased T cell sensitivity, while specifically inhibiting miR-181a decreased the immune response.

The researchers concluded that miR-181a functions as a sensitivity "dial" throughout the life of a T cell. It can determine at what threshold a T cell is activated to attack. This is the first clear example of a role for miRNAs in immune response.

WHY THIS MATTERS: Abnormal T cell activity toward the body's own tissues underlies many autoimmune disorders, such as rheumatoid arthritis, multiple sclerosis and lupus. Inhibiting miR-181a function could be a way to block the overactive response involved in some of those disorders. The findings strengthen the general idea that drugs blocking microRNAs could be useful in therapy against diseases that involve microRNAs as they are identified.

STANFORD CONNECTION: Seven of the 10 authors are from Stanford; three are from Alnylam Pharmaceuticals. The first author is Qi-Jing Li, a postdoctoral scholar; the senior authors are Mark Davis, PhD, professor, and Chang-Zheng Chen, PhD, assistant professor, all in the Department of Microbiology and Immunology.

FIND THIS STUDY: Published in the April 6 issue of the journal Cell.