last updated April 2013
Maintaining a check on inflammation
A noncoding RNA prevents autoimmunity and cancer generation in mice
Tight regulation of inflammation prevents the body from attacking itself and keeps immune cells from the uncontrolled proliferation that may lead to cancer. Now, a team of researchers, led by David Baltimore, an A-IMBN advisor from the California Institute of Technology in the United States, reports that a small noncoding RNA called miR-146a constrains immune cell activation and proliferation in mice1.
Baltimore and colleagues investigated miR-146a because they had previously found that its expression in immune cells increased in response to bacterial antigens. In the current study, they generated mice lacking the miR-146a gene. They found that, compared with normal mice, the miR-146a-deficient mice were more sensitive to bacterial antigens: they generated more pro-inflammatory cytokines, and were more susceptible to bacteria-induced septic shock. They also demonstrated that overexpression of miR-146a in immune cells reduced pro-inflammatory cytokine production in response to bacterial antigens.
As the miR-146a-deficient mice aged, they developed autoimmune-like disease, where immune cells reacted against the animal’s own organs and caused tissue damage. The older miR-146a-deficient mice also developed tumors in lymphoid organs, such as the spleen, indicating uncontrolled proliferation of immune cells. These findings indicate that if miR-146a plays a role in autoimmunity or cancer in humans, it could provide a new therapeutic target for these diseases.