Person:
Bradley, Sean J.

Profile Picture

Email Address

AA Acceptance Date

Birth Date

Research Projects

Organizational Units

Job Title

Last Name

Bradley

First Name

Sean J.

Name

Bradley, Sean J.

Filters

2015 - 20162

Settings

Author's Publications: search.filters.isAuthorOfPublication.a0d8e08e-72e1-47df-b712-5050eba156f5

Search Results

Now showing 1 - 2 of 2
  • Thumbnail Image
    Publication
    T Cell Transcriptomes Describe Patient Subtypes in Systemic Lupus Erythematosus
    (Public Library of Science, 2015) Bradley, Sean J.; Suarez-Fueyo, Abel; Moss, David R.; Kyttaris, Vasileios; Tsokos, George
    Background: T cells regulate the adaptive immune response and have altered function in autoimmunity. Systemic Lupus Erythematosus (SLE) has great diversity of presentation and treatment response. Peripheral blood component gene expression affords an efficient platform to investigate SLE immune dysfunction and help guide diagnostic biomarker development for patient stratification. Methods: Gene expression in peripheral blood T cell samples for 14 SLE patients and 4 controls was analyzed by high depth sequencing. Unbiased clustering of genes and samples revealed novel patterns related to disease etiology. Functional annotation of these genes highlights pathways and protein domains involved in SLE manifestation. Results: We found transcripts for hundreds of genes consistently altered in SLE T cell samples, for which DAVID analysis highlights induction of pathways related to mitochondria, nucleotide metabolism and DNA replication. Fewer genes had reduced mRNA expression, and these were linked to signaling, splicing and transcriptional activity. Gene signatures associated with the presence of dsDNA antibodies, low complement levels and nephritis were detected. T cell gene expression also indicates the presence of several patient subtypes, such as having only a minimal expression phenotype, male type, or severe with or without induction of genes related to membrane protein production. Conclusions: Unbiased transcriptome analysis of a peripheral blood component provides insight on autoimmune pathophysiology and patient variability. We present an open source workflow and richly annotated dataset to support investigation of T cell biology, develop biomarkers for patient stratification and perhaps help indicate a source of SLE immune dysfunction.
  • Thumbnail Image
    Publication
    ICER is requisite for Th17 differentiation
    (Nature Publishing Group, 2016) Yoshida, Nobuya; Comte, Denis; Mizui, Masayuki; Otomo, Kotaro; Rosetti, Florencia; Mayadas, Tanya; Crispín, José C.; Bradley, Sean J.; Koga, Tomohiro; Kono, Michihito; Karampetsou, Maria P.; Kyttaris, Vasileios; Tenbrock, Klaus; Tsokos, George
    Inducible cAMP early repressor (ICER) has been described as a transcriptional repressor isoform of the cAMP response element modulator (CREM). Here we report that ICER is predominantly expressed in Th17 cells through the IL-6–STAT3 pathway and binds to the Il17a promoter, where it facilitates the accumulation of the canonical enhancer RORγt. In vitro differentiation from naive ICER/CREM-deficient CD4+ T cells to Th17 cells is impaired but can be rescued by forced overexpression of ICER. Consistent with a role of Th17 cells in autoimmune and inflammatory diseases, ICER/CREM-deficient B6.lpr mice are protected from developing autoimmunity. Similarly, both anti-glomerular basement membrane-induced glomerulonephritis and experimental encephalomyelitis are attenuated in ICER/CREM-deficient mice compared with their ICER/CREM-sufficient littermates. Importantly, we find ICER overexpressed in CD4+ T cells from patients with systemic lupus erythematosus. Collectively, our findings identify a unique role for ICER, which affects both organ-specific and systemic autoimmunity in a Th17-dependent manner.