βc receptor antagonism mitigates sarcoid granuloma formation by targeting inflammatory signals and aberrant lipid metabolism

ABSTRACT: This study investigates transcriptional responses in a mouse model of pulmonary sarcoidosis induced by vimentin challenge, followed by therapeutic intervention using the βc receptor targeting monoclonal antibody CSL311 (VIM-CSL311) or an isotype control (VIM-ISO). Naïve mice (SAL) served as controls. Female humanised βc transgenic (hβcTg) mice were used in the study. In total, 16 RNA-seq libraries were generated: 6 SAL controls (3 produced within the primary study and 3 obtained from a matched external study conducted under similar experimental conditions), 5 VIM-ISO samples, and 5 VIM-CSL311 samples. Fresh-frozen lung tissues were crushed in liquid nitrogen. RNA was extracted from the crushed lung tissue using a RNeasy Plus kit (Qiagen, Germany) according to manufacturer’s instructions. The extracted RNA was subsequently used for bulk RNA-seq by the Australian Genome Research Facility (AGRF, Melbourne, Australia). RNA purity and integrity were assessed using an Agilent TapeStation System (Agilent Technologies, US) prior to library construction with the Illumina Stranded mRNA Prep kit (Illumina, US). Twenty million 150-bp paired end reads were performed on the Illumina NovaSeq X plus platform, and primary sequence data was then generated with the Illumina DRAGEN BCL Convert 07.021.645.4.0.3 pipeline. The raw sequencing data was analysed in FastQC and trimmed using TrimGalore-0.6.7 to remove low-quality reads and adaptor sequences. The STAR aligner (v 2.7.4a) was used to map reads against the Mus musculus genome (Build version mm39) and featureCounts from the Subread package (v2.0.3) was used to generate the raw gene counts.

ORGANISM(S): Mus musculus (mouse)

SUBMITTER: Hao Wang 

PROVIDER: S-BSST2277 | biostudies-other |

REPOSITORIES: biostudies-other