Vanja Sisirak, Benjamin Sally, Vivette D’Agati, Wilnelly Martinez-Ortiz, Z. Birsin Özçakar, Joseph David, Ali Rashidfarrokhi, Ada Yeste, Casandra Panea, Asiya Seema Chida, Milena Bogunovic, Ivaylo I. Ivanov, Francisco J. Quintana, Inaki Sanz, Keith B. Elkon, Mustafa Tekin, Fatoş Yalçınkaya, Timothy J. Cardozo, Robert M. Clancy, Jill P. Buyon, Boris Reizis
Abstract
Antibodies to DNA and chromatin drive autoimmunity in systemic lupus erythematosus (SLE). Null mutations and hypomorphic variants of the secreted deoxyribonuclease DNASE1L3 are linked to familial and sporadic SLE, respectively. We report that DNASE1L3-deficient mice rapidly develop autoantibodies to DNA and chromatin, followed by an SLE-like disease. Circulating DNASE1L3 is produced by dendritic cells and macrophages, and its levels inversely correlate with anti-DNA antibody response. DNASE1L3 is uniquely capable of digesting chromatin in microparticles released from apoptotic cells. Accordingly, DNASE1L3-deficient mice and human patients have elevated DNA levels in plasma, particularly in circulating microparticles. Murine and human autoantibody clones and serum antibodies from human SLE patients bind to DNASE1L3-sensitive chromatin on the surface of microparticles. Thus, extracellular microparticle-associated chromatin is a potential self-antigen normally digested by circulating DNASE1L3. The loss of this tolerance mechanism can contribute to SLE, and its restoration may represent a therapeutic opportunity in the disease.
Pharmacology, Toxicology and Pharmaceutical Science
7
2%
Other
23
7%
Unknown
90
28%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 106. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 22 August 2024.
All research outputs
#424,927
of 26,591,670 outputs
Outputs from Cell
#2,250
of 17,570 outputs
Outputs of similar age
#7,901
of 356,532 outputs
Outputs of similar age from Cell
#37
of 188 outputs
Altmetric has tracked 26,591,670 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 98th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 17,570 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 61.4. This one has done well, scoring higher than 87% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 356,532 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 97% of its contemporaries.
We're also able to compare this research output to 188 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 80% of its contemporaries.
