Maintaining a check on inflammation

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.