DNA as a self-antigen: nature and regulation
C Soni, B Reizis - Current opinion in immunology, 2018 - Elsevier
C Soni, B Reizis
Current opinion in immunology, 2018•ElsevierHighlights•Cell-free DNA is present in normal conditions and is targeted by antibodies in
SLE.•Chromatin in microparticles from apoptotic cells is a potential self-antigen in
SLE.•DNases are critical to prevent DNA-induced inflammation and autoantibody
responses.•DNASE1L3 is a secreted DNase that digests extracellular chromatin and
prevents SLE.High-affinity antibodies to double-stranded DNA are a hallmark of systemic
lupus erythematosus (SLE) and are thought to contribute to disease flares and tissue …
SLE.•Chromatin in microparticles from apoptotic cells is a potential self-antigen in
SLE.•DNases are critical to prevent DNA-induced inflammation and autoantibody
responses.•DNASE1L3 is a secreted DNase that digests extracellular chromatin and
prevents SLE.High-affinity antibodies to double-stranded DNA are a hallmark of systemic
lupus erythematosus (SLE) and are thought to contribute to disease flares and tissue …
Highlights
- Cell-free DNA is present in normal conditions and is targeted by antibodies in SLE.
- Chromatin in microparticles from apoptotic cells is a potential self-antigen in SLE.
- DNases are critical to prevent DNA-induced inflammation and autoantibody responses.
- DNASE1L3 is a secreted DNase that digests extracellular chromatin and prevents SLE.
High-affinity antibodies to double-stranded DNA are a hallmark of systemic lupus erythematosus (SLE) and are thought to contribute to disease flares and tissue inflammation such as nephritis. Notwithstanding their clinical importance, major questions remain about the development and regulation of these pathogenic anti-DNA responses. These include the mechanisms that prevent anti-DNA responses in healthy subjects, despite the constant generation of self-DNA and the abundance of DNA-reactive B cells; the nature and physical form of antigenic DNA in SLE; the regulation of DNA availability as an antigen; and potential therapeutic strategies targeting the pathogenic DNA in SLE. This review summarizes current progress in these directions, focusing on the role of secreted DNases in the regulation of antigenic extracellular DNA.
Elsevier