The indoleamine 2,3‐dioxygenase (IDO) pathway controls allergy

Abstract

A series of recent studies have demonstrated that the immunoregulatory pathway of tryptophan catabolism, initiated by the enzyme indoleamine 2,3-dioxygenase (IDO), is a critical participant in allergic inflammation. Originally known for its regulatory function during pregnancy and during chronic inflammation in tumorigenesis and infection, the activity of IDO seems to positively modify the inflammatory state of atopy or allergy. The tryptophan degradation pathway is important for tolerance induction during systemic allergen immunotherapy. Here, we focus on recent findings that establish the IDO pathway as central to allergic inflammation.The indoleamine 2,3-dioxygenase (IDO) pathway has been found to contribute substantially to the control of allergic inflammation. Traditionally recognized for its immunomodulatory role in infection, pregnancy, autoimmunity, and neoplasia, the effect of IDO on allergy appears to be a another piece of puzzle in the 'hygiene hypothesis'. Early microbial exposure and thus the stimulation of the IDO pathway by distinct Toll-like receptors (TLR) may, together with other immunoregulatory pathways, shape the predisposition to and determine the outcome of allergic inflammation, autoimmunity, and probably other diseases. Current data suggest that a normal induction of IDO activity, which decreases serum tryptophan (trp) levels and increases the levels of trp metabolites, controls the allergic inflammation. The mechanism of IDO-induced tolerance induction can probably be manifold but the induction of regulatory T cells may be a major aspect of the control function over allergic inflammation. This review summarizes the current knowledge on the IDO pathway and its role in regulating immune functions with a focus on allergic diseases.Tryptophan and its degradation pathways: indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase (TDO)As an essential amino acid, tryptophan (trp) is a constituent of proteins. Inadequate dietary intake of trp and other essential amino acids can lead to a negative nitrogen balance and to a loss of muscle mass, brain size, and weight (1). Trp is an essential starting point of two biochemical pathways: (i) the enzyme tryptophan 5-hydroxylase converts trp into 5-hydroxytryptophan, which is subsequently decarboxylized to 5-hydroxytryptamine (5-HT, serotonin), an essential neurotransmitter and vasoconstrictor, and (ii) two atoms of the molecular oxygen are inserted into L-trp to form N-formylkynurenine, the first and rate-limiting step in the kynurenine pathway (Fig. 1) (2, 3). The activation of molecular oxygen and its insertion into trp are catalyzed by three

Allergenic Can f 1 and its human homologue Lcn‐1 direct dendritic cells to induce divergent immune responses

“…One indicator for T-helper cell subtype induction is the IDO pathway for tryptophan breakdown 29. Tryptophan and kynurenine concentrations in supernatants of human monocyte-derived DCs were measured and found to be significantly lower in DCs treated with Can f 1 as compared to DCs treated with Lcn-1 (Fig.…”

Function and Therapeutic Potential of Mesenchymal Stem Cells in Atherosclerosis

“…Indoleamine-pyrrole-2-3-dioxygenase (IDO), an intracellular enzyme, is the primary mediator of MSC immunomodulatory activity. IDO has been shown to reduce immune cell proliferation by regulating tryptophan depletion and accumulating metabolites such as kynurenine (57, 58). MSCs are also known to halt B-cell maturation in G0/G1 phase and simultaneously diminish their chemotactic activity.…”

1-Methyl-tryptophan synergizes with methotrexate to alleviate arthritis in a mouse model of arthritis

“…The chief functional paradigm has been that IDO acts by suppressing T cell activation, prompting the general assumption that IDO inhibition would exacerbate autoimmune disorders (12, 13). However, studies using preclinical models of RA, asthma, and allergy suggest that the IDO pathway instead drives inflammation in certain pathological settings (7, 14, 15). Furthermore, RA patients exhibit elevated levels tryptophan catabolism that correlate with disease severity, suggesting that IDO may also contribute to pathogenicity in RA patients (16, 17).…”