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J Exp Med. 2012 Oct 22;209(11):2127-35. doi: 10.1084/jem.20120408. Epub 2012 Sep 24.

Tryptophan hydroxylase-1 regulates immune tolerance and inflammation.

Author information

1
Department of Microbiology and Immunology, Dartmouth Medical School and the Norris Cotton Cancer Center, Lebanon, NH 03756, USA.

Abstract

Nutrient deprivation based on the loss of essential amino acids by catabolic enzymes in the microenvironment is a critical means to control inflammatory responses and immune tolerance. Here we report the novel finding 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 deficiency breaks allograft tolerance, induces tumor remission, and intensifies neuroinflammation, respectively. All of these effects of Tph-1 deficiency 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 mechanism of MC-mediated immune suppression that broadly impacts multiple arms of immunity.

PMID:
23008335
PMCID:
PMC3478935
DOI:
10.1084/jem.20120408
[Indexed for MEDLINE]
Free PMC Article

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