Nav: Home

Baylor study reveals role for oxidized mitochondrial DNA in lupus

April 18, 2016

Researchers at the Baylor Institute for Immunology Research have discovered that the neutrophils of systemic lupus erythematosus (SLE) patients release oxidized DNA from their mitochondria that can stimulate an unwanted immune response. The study "Oxidized mitochondrial nucleoids released by neutrophils drive type I interferon production in human lupus," which will be published online April 18 in The Journal of Experimental Medicine, suggests that targeting the pathways that lead to the accumulation of this DNA and/or facilitate its removal could be new ways to treat this chronic autoimmune disease.

SLE is a common autoimmune disorder in which the body's immune system mistakenly attacks healthy tissues. Though the initial trigger for the disease remains unknown, it is characterized by the generation of autoantibodies that recognize the patient's own DNA or RNA-protein complexes and the excessive production of type I interferons, signaling proteins that activate the body's immune response. Virginia Pascual and colleagues at the Baylor Institute for Immunology Research in Dallas, Texas, previously discovered that SLE patient neutrophils--a type of immune cell--respond to certain autoantibodies by extruding some of their DNA, which subsequently stimulates another type of immune cell, called plasmacytoid dendritic cells, to produce type I interferons.

The paper by Simone Caielli and colleagues now reveals that SLE neutrophils accumulate oxidized DNA within their mitochondria and eventually extrude it from the cell to potently stimulate the production of interferons by plasmacytoid dendritic cells. Mitochondria are the cell's energy-generating organelles, and they contain their own DNA packaged up into structures called nucleoids. The researchers discovered that, to safely rid themselves of oxidized mitochondrial DNA, neutrophils usually disassemble their nucleoids and transfer the oxidized DNA to the cell's lysosomes for degradation. However, when SLE neutrophils are exposed to certain autoantibodies, nucleoid disassembly is impaired, and the oxidized DNA is retained inside mitochondria before eventually being extruded from the cell to stimulate interferon production. SLE patients also generated antibodies against the extruded, oxidized mitochondrial DNA, Caielli et al. found.

Oxidized mitochondrial DNA released from neutrophils therefore induces an immune response and may contribute to SLE pathogenesis. "Therapeutic efforts to enhance pathways involved in oxidized mitochondrial DNA degradation should be explored in human SLE, a disease for which only one new drug has been approved in the past 50 years," says Pascual.
-end-
Caielli, S., et al. 2016. J Exp. Med.http://dx.doi.org/10.1084/jem.20151876

About The Journal of Experimental Medicine

The Journal of Experimental Medicine (JEM)) is published by The Rockefeller University Press. All editorial decisions on submitted manuscripts are made by research-active scientists in conjunction with our in-house scientific editors. JEM provides free online access to many article types immediately, with complete archival content freely available online since the journal's inception. Authors retain copyright of their published works, and third parties may reuse the content for non-commercial purposes under a Creative Commons license. For more information, please visit jem.org. Follow us on Twitter at @JExpMed and @RockUPress.

Rockefeller University Press

Related Dna Articles:

Scientists now know what DNA's chaperone looks like
Researchers have discovered the structure of the FACT protein -- a mysterious protein central to the functioning of DNA.
In one direction or the other: That is how DNA is unwound
DNA is like a book, it needs to be opened to be read.
DNA is like everything else: it's not what you have, but how you use it
A new paradigm for reading out genetic information in DNA is described by Dr.
A new spin on DNA
For decades, researchers have chased ways to study biological machines.
From face to DNA: New method aims to improve match between DNA sample and face database
Predicting what someone's face looks like based on a DNA sample remains a hard nut to crack for science.
Self-healing DNA nanostructures
DNA assembled into nanostructures such as tubes and origami-inspired shapes could someday find applications ranging from DNA computers to nanomedicine.
DNA design that anyone can do
Researchers at MIT and Arizona State University have designed a computer program that allows users to translate any free-form drawing into a two-dimensional, nanoscale structure made of DNA.
DNA find
A Queensland University of Technology-led collaboration with University of Adelaide reveals that Australia's pint-sized banded hare-wallaby is the closest living relative of the giant short-faced kangaroos which roamed the continent for millions of years, but died out about 40,000 years ago.
DNA structure impacts rate and accuracy of DNA synthesis
DNA sequences with the potential to form unusual conformations, which are frequently associated with cancer and neurological diseases, can in fact slow down or speed up the DNA synthesis process and cause more or fewer sequencing errors.
Changes in mitochondrial DNA control how nuclear DNA mutations are expressed in cardiomyopathy
Differences in the DNA within the mitochondria, the energy-producing structures within cells, can determine the severity and progression of heart disease caused by a nuclear DNA mutation.
More Dna News and Dna Current Events

Top Science Podcasts

We have hand picked the top science podcasts of 2019.
Now Playing: TED Radio Hour

In & Out Of Love
We think of love as a mysterious, unknowable force. Something that happens to us. But what if we could control it? This hour, TED speakers on whether we can decide to fall in — and out of — love. Guests include writer Mandy Len Catron, biological anthropologist Helen Fisher, musician Dessa, One Love CEO Katie Hood, and psychologist Guy Winch.
Now Playing: Science for the People

#543 Give a Nerd a Gift
Yup, you guessed it... it's Science for the People's annual holiday episode that helps you figure out what sciency books and gifts to get that special nerd on your list. Or maybe you're looking to build up your reading list for the holiday break and a geeky Christmas sweater to wear to an upcoming party. Returning are pop-science power-readers John Dupuis and Joanne Manaster to dish on the best science books they read this past year. And Rachelle Saunders and Bethany Brookshire squee in delight over some truly delightful science-themed non-book objects for those whose bookshelves are already full. Since...
Now Playing: Radiolab

An Announcement from Radiolab