3-Hydroxyanthranilic acid inhibits PDK1 activation and suppresses experimental asthma by inducing T cell apoptosis
- 20 November 2007
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 104 (47), 18619-18624
- https://doi.org/10.1073/pnas.0709261104
Abstract
3-Hydroxyanthranilic acid (HAA), a compound generated during tryptophan metabolism initiated by indoleamine 2,3-dioxygenase, is known to induce T cell death, but its molecular target is not known. Here we report that HAA inhibits NF-κB activation upon T cell antigen receptor engagement by specifically targeting PDK1. Inhibition of NF-κB by HAA leads to dysfunction and cell death of activated Th2 cells, which in turn suppresses experimental asthma. Inhibition of NF-κB and induction of apoptosis is specific to CD4 T cells because HAA does not inhibit NF-κB activation or induce cell death upon Toll-like receptor 4 stimulation in dendritic cells. Thus, HAA is a natural inhibitor that restrains T cell expansion and activation.Keywords
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