The Journal of Experimental Medicine
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.
Nowak, Elizabeth C.; de Vries, Victor C.; Wasiuk, Anna; Ahonen, Cory; Bennett, Kathryn A.; LE Mercier, Isabelle; Ha, Dae-Gon; and Noelle, Randolph J., "Tryptophan Hydroxylase-1 Regulates Immune Tolerance and Inflammation" (2012). Open Dartmouth: Faculty Open Access Articles. 1246.