The tryptophan catabolic enzyme indoleamine 2,3-dioxygenase (IDO) has emerged as an important driver of immune escape in a growing number of cancers and cancer-associated chronic infections. In this study, we define novel immunotherapeutic applications for the heme precursor compound zinc protoporphyrin IX (ZnPP) based on our discovery that it is a potent small-molecule inhibitor of IDO. Inhibi...

Indoleamine 2,3-dioxygenase (IDO), a potent immunosuppressive enzyme, contributes to tumoral escape, immune tolerance, and protection against allograft injury. In this paper, we report that inhibition of CD8(+) T cell-mediated cytotoxic function is an important mechanism behind IDO's immune-modulating property. The experimental rat lung allograft proved attractive for evaluating effector CD8(+)...

Indolemine 2, 3-dioxygenase (IDO) is a cytosolic monomeric hemoprotein enzyme that catalyses tryptophan, the least available essential amino acid in the human body, to N-formylkynurenine, which in turn rapidly degrades to give kynurenine. IDO is expressed in different tissues, especially and prominently in some subsets of antigen presenting cells (APCs) of lymphoid organs and also in the placen...

RATIONALE Indoleamine 2,3-dioxygenase (IDO) induces generation of regulatory T cells but suppresses Th17 cells and therefore might attenuate neutrophilic inflammation. The role of IDO in neutrophilic airway diseases such as chronic obstructive pulmonary disease (COPD) remains unknown. We evaluated IDO activity and expression and interleukin (IL)-10 and IL-17A levels in sputum from patients with...

The immunoregulatory enzyme indoleamine 2,3-dioxygenase (IDO) is expressed by a subset of murine plasmacytoid DCs (pDCs) in tumor-draining lymph nodes (TDLNs), where it can potently activate Foxp3+ regulatory T cells (Tregs). We now show that IDO functions as a molecular switch in TDLNs, maintaining Tregs in their normal suppressive phenotype when IDO was active, but allowing inflammation-induc...

IDO is the rate-limiting enzyme in the kynurenine pathway, catabolizing tryptophan to kynurenine. Tryptophan depletion by IDO-expressing tumors is a common mechanism of immune evasion inducing regulatory T cells and inhibiting effector T cells. Because mammalian cells cannot synthesize tryptophan, it remains unclear how IDO(+) tumor cells overcome the detrimental effects of local tryptophan dep...

Indoleamine 2,3 dioxygenase (IDO) has emerged as an important mediator of immune tolerance via inhibition of Th1 responses. However, the role of IDO in antigen-induced tolerance or allergic inflammation in the airways that is regulated by Th2 responses has not been elucidated. By using IDO(-/-) mice, we found no impairment of airway tolerance, but, surprisingly, absence of IDO provided signific...

The heme protein indoleamine 2,3-dioxygenase (IDO) is induced by the proinflammatory cytokine interferon-gamma (IFNgamma) and plays an important role in the immune response by catalyzing the oxidative degradation of L-tryptophan (Trp) that contributes to immune suppression and tolerance. Here we examined the mechanism by which nitric oxide (NO) inhibits human IDO activity. Exposure of IFNgamma-...

Systemic sclerosis (SSc) is characterized by tissue fibrosis, vasculopathy and autoimmunity. Indoleamine 2,3 dioxygenase (IDO) plays a pivotal role in immunological tolerance modulating regulatory T cell (Treg) generation and function. Single nucleotide polymorphisms (SNPs) of IDO gene could impact on Treg function and predispose to autoimmunity. Here, the existence of an association between sp...

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor initially identified because of its role in controlling the cellular response to environmental molecules. More recently, AHR has been shown to play a crucial role in controlling innate and adaptive immune responses through several mechanisms, one of which is the regulation of tryptophan metabolism. Indoleamine-2,3-di...