| First Author | Costanza M | Year | 2019 |
| Journal | Proc Natl Acad Sci U S A | Volume | 116 |
| Issue | 18 | Pages | 8985-8994 |
| PubMed ID | 30988194 | Mgi Jnum | J:274659 |
| Mgi Id | MGI:6297152 | Doi | 10.1073/pnas.1822013116 |
| Citation | Costanza M, et al. (2019) DNA threads released by activated CD4(+) T lymphocytes provide autocrine costimulation. Proc Natl Acad Sci U S A 116(18):8985-8994 |
| abstractText | 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. |
