Disruption of diacylglycerol metabolism impairs the induction of T cell anergy View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2006-11

AUTHORS

Benjamin A Olenchock, Rishu Guo, Jeffery H Carpenter, Martha Jordan, Matthew K Topham, Gary A Koretzky, Xiao-Ping Zhong

ABSTRACT

Anergic T cells have altered diacylglycerol metabolism, but whether that altered metabolism has a causative function in the induction of T cell anergy is not apparent. To test the importance of diacylglycerol metabolism in T cell anergy, we manipulated diacylglycerol kinases (DGKs), which are enzymes that terminate diacylglycerol-dependent signaling. Overexpression of DGK-alpha resulted in a defect in T cell receptor signaling that is characteristic of anergy. We generated DGK-alpha-deficient mice and found that DGK-alpha-deficient T cells had more diacylglycerol-dependent T cell receptor signaling. In vivo anergy induction was impaired in DGK-alpha-deficient mice. When stimulated in anergy-producing conditions, T cells lacking DGK-alpha or DGK-zeta proliferated and produced interleukin 2. Pharmacological inhibition of DGK-alpha activity in DGK-zeta-deficient T cells that received an anergizing stimulus proliferated similarly to wild-type T cells that received CD28 costimulation and prevented anergy induction. Our findings suggest that regulation of diacylglycerol metabolism is critical in determining whether activation or anergy ensues after T cell receptor stimulation. More... »

PAGES

1174-1181

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ni1400

DOI

http://dx.doi.org/10.1038/ni1400

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1053206259

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/17028587


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Download the RDF metadata as:  json-ld nt turtle xml License info

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Turtle is a human-readable linked data format.

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