Abstract
Altered CD4+ T cell Transcriptional and Epigenetic Programming Define Changes in Sarcoidosis Disease Phenotypes
The Journal of immunology (1950), Vol.204(1_Supplement), pp.224-224.42
05/01/2020
DOI: 10.4049/jimmunol.204.Supp.224.42
Abstract
Abstract Sarcoidosis is an inflammatory disease, which is characterized by granulomas in the lungs, extrapulmonary inflammation, and can cause death by lung fibrosis. It is known that CD4+ T cell lung population increases in Sarcoidosis. However, the immunopathology remains unclear and no biomarker has been identified. Here we use RNA-seq to examine gene expression in CD4+ T cells of differential Sarcoidosis phenotypes and healthy donors. Our data showed that BATF, a Tfh inducer/key factor in Th17 differentiation was up-regulated while BCL6, a Th17 repressor is down-regulated in RNA-seq. IRF4 and BCL6 were identified as potential transcriptional upstream regulators using IPA. IL-4 and fibrosis related genes were differentially expressed with altered disease phenotype, indicating that type 2 immune response may participate in disease phenotype progression for development of fibrosis. In addition, we used ChIP-seq and ATAC-seq to examine genome-wide epigenetic histone signatures and global chromatin accessibility associated with Sarcoidosis phenotypes. TF binding-site analysis of ATAC-seq peaks revealed an enrichment of BATF binding motifs, highlighting the utility of integrating epigenetic and transcriptional signatures to suggest molecular drivers of Sarcoidosis. Our findings identified several potential immune related biomarkers and molecular mechanisms that may drive disease progression.
Details
- Title: Subtitle
- Altered CD4+ T cell Transcriptional and Epigenetic Programming Define Changes in Sarcoidosis Disease Phenotypes
- Creators
- Ting-Hui Clair Tu - National Jewish HealthJennifer Knapp - National Jewish HealthLaura Harmacek - National Jewish HealthRoman Magallon - National Jewish HealthBrian Vestal - National Jewish HealthSonia Leach - National Jewish HealthThomas Danhorn - National Jewish HealthLily Li - National Jewish HealthMay Gillespie - National Jewish HealthKristyn MacPhail - National Jewish HealthChristina Riley - National Jewish HealthBriana Barkes - National Jewish HealthJill Elliott - National Jewish HealthNicholas Arger - 3Dept. of Medicine, UCSFAnne Sommer - 3Dept. of Medicine, UCSFLinda Powers - University of IowaBrenda Werner - University of IowaTasha Fingerlin - National Jewish HealthLisa Maier - National Jewish HealthLaura Koth - 3Dept. of Medicine, UCSFNabeel Hamzeh - University of IowaBrian O’Connor - National Jewish Health
- Resource Type
- Abstract
- Publication Details
- The Journal of immunology (1950), Vol.204(1_Supplement), pp.224-224.42
- DOI
- 10.4049/jimmunol.204.Supp.224.42
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Language
- English
- Date published
- 05/01/2020
- Academic Unit
- Pulmonary, Critical Care, and Occupational Medicine; Internal Medicine
- Record Identifier
- 9984362354802771
Metrics
2 Record Views