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J Neuroimmunol. 2012 May 15;246(1-2):51-7. doi: 10.1016/j.jneuroim.2012.03.003. Epub 2012 Mar 27.

Increased promoter methylation of the immune regulatory gene SHP-1 in leukocytes of multiple sclerosis subjects.

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Department of Microbiology & Immunology, SUNY Upstate Medical University, Syracuse, NY 13210, USA.


The protein tyrosine phosphatase, SHP-1, is a negative regulator of proinflammatory signaling and autoimmune disease. We have previously reported reduced SHP-1 expression in peripheral blood leukocytes of subjects with multiple sclerosis (MS). Recent evidence indicates that virus-induced DNA methylation of the SHP-1 promoter is responsible for aberrant silencing of SHP-1 expression and function in hematopoietic cells that might relate to inflammatory diseases. In the present study, bisulfite sequencing of the SHP-1 promoter demonstrated that over a third of MS subjects had abnormally high promoter methylation. As SHP-1 is deficient in MS leukocytes and SHP-1-regulated proinflammatory genes are correspondingly upregulated, we propose that increased SHP-1 promoter methylation may relate in part to decreased SHP-1 expression and increased leukocyte-mediated inflammation in MS.

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