Superfund Research Program
Nuclear Receptor Mediated Epigenetic and Immune Cell Changes in Liver Fibrosis Resulting From Toxicant Exposure
Project Leader: Ronald M. Evans (Salk Institute for Biological Studies)
Co-Investigator: Michael Downes (Salk Institute for Biological Studies)
Grant Number: P42ES010337
Funding Period: 2017-2023
Project-Specific Links
- Project Summary
Title: Circadian Clock Protein CRY Regulates Autoimmunity
Accession Number: GSE87467
Link to Dataset: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE87467
Repository: Gene Expression Omnibus (GEO)
Data Type(s): Gene Expression
Experiment Type(s): Expression profiling by array
Organism(s): Mus musculus
Summary: The circadian system regulates numerous physiological processes including the adaptive immune system. Here we show that mice deficient for the circadian genes Cry1 and Cry2, (DKO) display an autoimmune phenotype including higher serum IgG concentration, presence of serum anti-nuclear antibodies, precipitation of IgG, IgM and complement 3 in glomeruli, and massive infiltrations of leukocytes into the lung and kidney. Activation of Cry DKO splenic B cells elicited markedly enhanced and prolonged tyrosine phosphorylation of cellular proteins compared to cells from control mice, suggesting that over activation of the BCR signaling pathway may contribute to autoimmunity in the Cry DKO mice. Expression of C1q, deficiency of which contributes to the pathogenesis of Systemic lupus erythematosus (SLE), was significantly downregulated in Cry DKO B cells. This suggests that B cell development, BCR signaling pathway and C1q expression may be under direct circadian control and dysregulation of which contributes to autoimmunity.
Publication(s) associated with this dataset:- Cao Q, Zhao X, Bai J, Gery S, Sun H, Lin D, Chen Q, Chen Z, Mack L, Yang H, Deng R, Shi X, Chong L, Cho H, Xie J, Li Q, Muschen M, Atkins AR, Liddle C, Yu RT, Alkan S, Said JW, Zheng Y, Downes M, Evans RM, Koeffler HP. 2017. Circadian clock cryptochrome proteins regulate autoimmunity. Proc Natl Acad Sci U S A 114(47):12548-12553. doi:10.1073/pnas.1619119114 PMID:29109286 PMCID:PMC5703267