{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T13:37:57Z","timestamp":1791293877762,"version":"4.1.0"},"reference-count":32,"publisher":"Rockefeller University Press","issue":"11","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2012,10,22]]},"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.1084\/jem.20120408","type":"journal-article","created":{"date-parts":[[2012,9,24]],"date-time":"2012-09-24T22:35:31Z","timestamp":1348526131000},"page":"2127-2135","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":119,"title":["Tryptophan hydroxylase-1 regulates immune tolerance and inflammation"],"prefix":"10.1084","volume":"209","author":[{"given":"Elizabeth C.","family":"Nowak","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Dartmouth Medical School and the Norris Cotton Cancer Center, Lebanon, NH 03756 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor C.","family":"de Vries","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Dartmouth Medical School and the Norris Cotton Cancer Center, Lebanon, NH 03756 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Wasiuk","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Dartmouth Medical School and the Norris Cotton Cancer Center, Lebanon, NH 03756 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cory","family":"Ahonen","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Dartmouth Medical School and the Norris Cotton Cancer Center, Lebanon, NH 03756 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn A.","family":"Bennett","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Dartmouth Medical School and the Norris Cotton Cancer Center, Lebanon, NH 03756 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Le Mercier","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Dartmouth Medical School and the Norris Cotton Cancer Center, Lebanon, NH 03756 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dae-Gon","family":"Ha","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Dartmouth Medical School and the Norris Cotton Cancer Center, Lebanon, NH 03756 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randolph J.","family":"Noelle","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Dartmouth Medical School and the Norris Cotton Cancer Center, Lebanon, NH 03756 1"},{"name":"Medical Research Council Centre for Transplantation, Guy\u2019s Hospital, King\u2019s College London, King\u2019s Health Partners, London SE1 9RT, England, UK 2"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2012,9,24]]},"reference":[{"key":"2023072600473730000_bib1","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1172\/JCI0215751","article-title":"Experimental autoimmune encephalitis and inflammation in the absence of interleukin-12","volume":"110","author":"Becher","year":"2002","journal-title":"J. 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