Oxidized Mitochondrial DNA from Immune Cells Enhances Damaging Effects of Lupus, Researchers Say

Patricia Inacio, PhD avatar

by Patricia Inacio, PhD |

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Oxidized mitochondrial DNA

In a new study, researchers at the Baylor Institute for Immunology Research in Dallas, Texas, showed that immune cells, called neutrophils, in patients with systemic lupus erythematosus (SLE) release oxidized DNA from their mitochondria, stimulating a damaging immune response. Therapies targeting the pathway that lead to the accumulation of this DNA, or finding those promoting its removal, could be potential new treatments for SLE, according to the research.

The study, “Oxidized mitochondrial nucleoids released by neutrophils drive type I interferon production in human lupus,” was published online in The Journal of Experimental Medicine.

SLE is an autoimmune disease characterized by the production of autoantibodies which are produced by the immune system and mistakenly target and react against our own tissues or organs, therefore failing to distinguish between “self” and “non-self.” In systemic lupus erythematosus, the generated autoantibodies mainly target nuclear components, particularly chromatin (a complex of DNA and proteins that forms chromosomes within the nucleus of cells).

The team of researchers had previously shown that neutrophils of SLE patients respond to certain autoantibodies by ejecting part of their DNA. This response stimulates other immune cells that initiate an inflammatory response, specifically mediated by type 1 interferons.

Now, the team led by Simone Caielli and Virginia Pascual at Baylor discovered that in SLE, neutrophils accumulate oxidized DNA within their mitochondria (the cell’s energy-generating organelles) and eventually extrude it from the cell to stimulate type 1 interferon production by plasmacytoid dendritic cells.

Researchers also found that SLE patients react to the extruded, oxidized mitochondrial DNA by producing autoantibodies to protect themselves against it.

The results showed that oxidized mitochondrial DNA released from neutrophils induces an inflammatory response, which may aggravate the pathogenesis of SLE.

“Therapeutic efforts to enhance pathways involved in oxidized mitochondrial DNA degradation should be explored in human systemic lupus erythematosus, a disease for which only one new drug has been approved in the past 50 years,” said Pascual, the study’s lead author, in a press release.