Document Type

Article

Publication Date

8-24-2012

Publication Title

The Journal of Experimental Medicine

Department

Geisel School of Medicine

Abstract

Nutrient deprivation based on the loss of essential amino acids by catabolic enzymes in the microenvironment is a critical means to control in ammatory responses and immune tolerance. Here we report the novel nding that Tph-1 (tryptophan hydroxylase-1), a synthase which catalyses the conversion of tryptophan to serotonin and exhausts tryptophan, is a potent regulator of immunity. In models of skin allograft tolerance, tumor growth, and experimental autoimmune encephalomyelitis, Tph-1 de ciency breaks allograft tolerance, induces tumor remission, and intensi es neuroin ammation, respectively. All of these effects of Tph-1 de ciency are independent of its downstream product serotonin. Because mast cells (MCs) appear to be the major source of Tph-1 and restoration of Tph-1 in the MC compartment in vivo compensates for the defect, these experiments introduce a fundamentally new mecha- nism of MC-mediated immune suppression that broadly impacts multiple arms of immunity.

DOI

10.1084/jem.20120408

Original Citation

Nowak EC, de Vries VC, Wasiuk A, Ahonen C, Bennett KA, Le Mercier I, Ha DG, Noelle RJ. Tryptophan hydroxylase-1 regulates immune tolerance and inflammation. J Exp Med. 2012 Oct 22;209(11):2127-35. doi: 10.1084/jem.20120408. Epub 2012 Sep 24. PMID: 23008335; PMCID: PMC3478935.

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