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National Academy of Sciences, Proceedings of the National Academy of Sciences, 47(104), p. 18619-18624, 2007

DOI: 10.1073/pnas.0709261104

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3-Hydroxyanthranilic acid inhibits PDK1 activation and suppresses experimental asthma by inducing T cell apoptosis

Journal article published in 2007 by Tomoko Hayashi, Ji-Hun Mo ORCID, Xing Gong, Cyprian Rossetto, Angela Jang, Lucinda Beck, Gregory I. Elliott, Irina Kufareva, Ruben Abagyan, David H. Broide ORCID, Jongdae Lee, Eyal Raz
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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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.