期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 104, 期 47, 页码 18619-18624出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0709261104
关键词
HAA; indoleamine 2,3-dioxygenase; NF-kappa B; tryptophan
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-kappa B activation upon T cell antigen receptor engagement by specifically targeting PDK1. Inhibition of NF-kappa B by HAA leads to dysfunction and cell death of activated Th2 cells, which in turn suppresses experimental asthma. Inhibition of NF-kappa B and induction of apoptosis is specific to CD4 T cells because HAA does not inhibit NF-kappa B 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.
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