期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 209, 期 11, 页码 2127-2135出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20120408
关键词
-
资金
- National Institutes of Health [A1084089, CA123079, A1048667]
- Medical Research Council Centre for Transplantation and Biomedical Research Center at King's College London
- National Multiple Sclerosis Society
- MRC [G0802651] Funding Source: UKRI
- Medical Research Council [G0802651, G0600698B, MR/J006742/1] Funding Source: researchfish
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据