Transcriptomics

Dataset Information

295

Loss of Trex1 in dendritic cells is sufficient to trigger systemic autoimmunity


ABSTRACT: Biallelic defects of the gene encoding for the intracellular enzyme 3’ repair exonuclease (Trex)1 cause Aicardi-Goutières syndrome (AGS), a rare monogenic, lupus-like autoimmune disease, while heterozygous Trex1 loss of function alleles are associated with systemic lupus erythematosus (SLE). Trex1-/- mice develop lethal autoimmune multi-organ inflammation, which results from a chronic type I IFN response triggered by intracellular accumulation of a putative nucleic acid substrate of Trex1. This pathogenic nucleic acid is detected by the broadly, but not ubiquitously, expressed cytosolic DNA sensor cGAS, raising the question whether there are specific cell types that respond to Trex1 deficiency by production of IFN and induce autoimmunity. We generated mice with conditional knock out of the Trex1 gene and demonstrated that loss of Trex1 throughout the hematopoietic system and even selective loss in dendritic cells is sufficient to cause IFN release and autoimmunity. B cells showed no transcriptional response to Trex1 deficiency. Trex1-/- keratinocytes produced IFN but did not induce skin inflammation, whereas loss of Trex1 in cardiomyocytes triggered neither IFN response nor pathology. Trex1-deficient neurons and astrocytes did not release IFN in the CNS. In contrast, mice with selective inactivation of Trex1 in long-living CNS macrophages such as microglia locally produced IFN but did not reproduce the mild encephalitis seen in Trex1-/- mice. Collectively, individual cell types differentially respond to the loss of Trex1 and dendritic cells seem promising candidates for experiments addressing the molecular pathomechanism in Trex1 deficiency. We sorted CD19-positive B cells from spleens of Trex1fl/fl CD19-Cre+ and Trex1fl/fl CD19-Cre- mice and isolated total RNA for library construction to perform mRNA deep sequencing.

ORGANISM(S): Mus musculus  

SUBMITTER: Axel Roers   Rayk Behrendt  Mathias Lesche  Katrin Peschke  Andreas Dahl 

PROVIDER: E-GEOD-77693 | ArrayExpress | 2016-08-01

SECONDARY ACCESSION(S): GSE77693SRP069804PRJNA311280

REPOSITORIES: GEO, ArrayExpress, ENA

Similar Datasets

2016-10-21 | E-GEOD-77784 | ArrayExpress
2016-07-27 | E-GEOD-75775 | ArrayExpress
2015-04-21 | E-GEOD-68083 | ArrayExpress
2015-07-10 | E-GEOD-70706 | ArrayExpress
2016-02-08 | E-GEOD-76359 | ArrayExpress
2016-03-02 | E-GEOD-76217 | ArrayExpress
2015-08-03 | E-GEOD-64113 | ArrayExpress
2016-07-30 | E-GEOD-77351 | ArrayExpress
2014-08-04 | E-GEOD-57500 | ArrayExpress
2015-04-27 | E-GEOD-67610 | ArrayExpress