Leading the way to a cure


Innate Sensing of AT-rich DNA During Autoimmunity

Sharma, Shruti, PhD

University of Massachusetts Medical School

Numerous immune system components contribute to disease development and progression in lupus. These include toll-like receptors (TLR), particularly TLR7 and TLR9. These proteins recognize RNA or DNA from dying cells and trigger inflammation in lupus patients by activating immune cells such as dendritic and B cells. Dendritic cells produce inflammatory molecules called type I interferons while B cells generate autoantibodies that eventually cause organ damage in the later stages of the disease. 

With their ALR grant, Dr. Sharma and her colleague, Dr. Fitzgerald hope to discover what triggers autoimmune diseases like lupus and rheumatoid arthritis (RA). They suspect that the DNA released from dying cells contains clues to this event. Specifically, it appears that the location of the DNA may affect the disease differently than we initially thought. For instance, in autoimmune diseases like RA, abnormal DNA accumulates within cells and triggers pathways independently of TLR activation. Similarly, in lupus it appears that a different pathway operating separately from TLR9 activation may be responsible for the initial production of interferons, exacerbating subsequent symptoms and organ damage. This pathway may be related to the “nature” of the accumulated DNA. In other words, the location of the DNA within the cell and the enrichment of certain parts of the DNA could provide a clue as to its role in the disease. 

The researchers also plan to use complex genetic models to investigate specific proteins involved in detecting this buildup of DNA.

What this study means for people with lupus: This research can help identify important and novel targets and pathways in the development and progression of lupus that could lead to new therapeutic targets.

1.5 million

people in the U.S. have Lupus.

172 million

dollars committed to lupus research by the Lupus Research Alliance.

We're walking across the United States to raise awareness and funds for lupus research.


Show your support by visiting the Lupus Research Alliance online store. Discover the perfect gift, or prepare for a walk with our selection of apparel and accessories.

Powered by Blackbaud
nonprofit software