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.
机构:
Lankenau Inst Med Res, Wynnewood, PA 19096 USA
Lankenau Hosp, Div Hematol Oncol, Dept Med, Wynnewood, PA USALankenau Inst Med Res, Wynnewood, PA 19096 USA
Katz, Jessica B.
Muller, Alexander J.
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机构:
Lankenau Inst Med Res, Wynnewood, PA 19096 USA
Thomas Jefferson Univ, Kimmel Canc Ctr, Philadelphia, PA 19107 USALankenau Inst Med Res, Wynnewood, PA 19096 USA
Muller, Alexander J.
Prendergast, George C.
论文数: 0引用数: 0
h-index: 0
机构:
Lankenau Inst Med Res, Wynnewood, PA 19096 USA
Thomas Jefferson Univ, Kimmel Canc Ctr, Philadelphia, PA 19107 USA
Thomas Jefferson Univ, Jefferson Med Sch, Philadelphia, PA 19107 USALankenau Inst Med Res, Wynnewood, PA 19096 USA
机构:
Lankenau Inst Med Res, Wynnewood, PA 19096 USA
Lankenau Hosp, Div Hematol Oncol, Dept Med, Wynnewood, PA USALankenau Inst Med Res, Wynnewood, PA 19096 USA
Katz, Jessica B.
Muller, Alexander J.
论文数: 0引用数: 0
h-index: 0
机构:
Lankenau Inst Med Res, Wynnewood, PA 19096 USA
Thomas Jefferson Univ, Kimmel Canc Ctr, Philadelphia, PA 19107 USALankenau Inst Med Res, Wynnewood, PA 19096 USA
Muller, Alexander J.
Prendergast, George C.
论文数: 0引用数: 0
h-index: 0
机构:
Lankenau Inst Med Res, Wynnewood, PA 19096 USA
Thomas Jefferson Univ, Kimmel Canc Ctr, Philadelphia, PA 19107 USA
Thomas Jefferson Univ, Jefferson Med Sch, Philadelphia, PA 19107 USALankenau Inst Med Res, Wynnewood, PA 19096 USA