Abstract
The extrusion of DNA traps contributes to a key mechanism in which innate immune cells clear pathogens or induce sterile inflammation. Here we provide evidence that CD4+ T cells, a critical regulator of adaptive immunity, release extracellular threads of DNA on activation. These DNA extrusions convey autocrine costimulatory signals to T lymphocytes and can be detected in lymph nodes isolated during the priming phase of experimental autoimmune encephalomyelitis (EAE), a CD4+ T cell-driven mouse model of multiple sclerosis. Pharmacologic inhibition of mitochondrial reactive oxygen species (mtROS) abolishes the extrusion of DNA by CD4+ T cells, reducing cytokine production in vitro and T cell priming against myelin in vivo. Moreover, mtROS blockade during established EAE markedly ameliorates disease severity, dampening autoimmune inflammation of the central nervous system. Taken together, these experimental results elucidate a mechanism of intrinsic immune costimulation mediated by DNA threads released by activated T helper cells, and identify a potential therapeutic target for such disorders as multiple sclerosis, neuromyelitis optica, and CD4+ T cell-mediated disorders.
Original language | English |
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Pages (from-to) | 8985-8994 |
Number of pages | 10 |
Journal | Proceedings of the National Academy of Sciences of the United States of America |
Volume | 116 |
Issue number | 18 |
DOIs | |
Publication status | Published - Apr 30 2019 |
Keywords
- Autoimmunity
- CD4 T cells
- DNA threads
- EAE
- Multiple sclerosis
ASJC Scopus subject areas
- General