Effect of indoleamine 2,3-dioxygenase on induction of experimental autoimmune encephalomyelitis

Indoleamine 2,3 dioxygenase–mediated tryptophan catabolism regulates accumulation of Th1/Th17 cells in the joint in collagen‐induced arthritis

“…This interpretation is supported by our finding that inhibition of IDO by 1-MT after arthritis onset exacerbates CIA. It is also consistent with a series of studies in EAE (12,13) and with a previous study by Szanto et al (14) demonstrating that inhibition of IDO before arthritis onset, but at a time when IDO up-regulation is observed, also exacerbated CIA.…”

“…tryptophan degradation by the nonspecific inhibitor 1-methyltryptophan (1-MT) exacerbates EAE and collagen-induced arthritis (CIA) (12)(13)(14). Conversely, administration of 3-DAA, a synthetic analog of the tryptophan metabolite 3-hydroxyanthranyllic acid, ameliorates EAE and CIA (15,16).…”

3-Hydroxyanthranilic acid inhibits PDK1 activation and suppresses experimental asthma by inducing T cell apoptosis

“…A derivative of HAA, N- (3,4,-dimethoxycinnamoyl) anthranilic acid, was shown to inhibit Th1-mediated experimental autoimmune encephalomyelitis. Another study showed that inhibition of IDO aggravated Th1-mediated colitis (9,10), and an in vitro study demonstrated a Th1 susceptibility to HAA (15). We demonstrated here that HAA inhibits CD4 cells (Th1, Th2, and Jurkat) regardless of their Th phenotype.…”

“…The immunomodulatory function of IDO was first identified in the placenta, where it inhibits the rejection of fetal allografts (2,4). Subsequent studies documented that IDO inhibits T cell proliferation in vitro (4,5), promotes the survival of allografts (6)(7)(8), and ameliorates both experimental autoimmune encephalomyelitis (9) and trinitrobenzenesulfonic acid-induced colitis (10).…”

Lipopolysaccharide-induced depressive-like behavior is mediated by indoleamine 2,3-dioxygenase activation in mice

“…10 Since its first characterization as a competitive inhibitor of IDO, 37 1-MT has become the compound of reference for IDO-blocking studies. 21,22,[38][39][40] Its ability to block IDO activation in response to LPS is demonstrated in the present study by the decreased kynurenine/ tryptophan ratio that is observed in both the periphery and the brain of 1-MT-treated mice. Since the main consequence of IDO activation is development of immunotolerance because of an inability of tryptophan-deprived T cells to proliferate and induce cytotoxicity, blockade of IDO has mainly been studied in the context of reproductive physiology and tumor immune surveillance.…”