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Review
. 2024 Mar 14:17:11786469241232871.
doi: 10.1177/11786469241232871. eCollection 2024.

Kynurenine Pathway in Respiratory Diseases

Guillaume Pamart  1 , Philippe Gosset  1 , Olivier Le Rouzic  1 , Muriel Pichavant  1 , Odile Poulain-Godefroy  1
Affiliations
Review

Kynurenine Pathway in Respiratory Diseases

Guillaume Pamart et al. Int J Tryptophan Res. .

Abstract

The kynurenine pathway is the primary route for tryptophan catabolism and has received increasing attention as its association with inflammation and the immune system has become more apparent. This review provides a broad overview of the kynurenine pathway in respiratory diseases, from the initial observations to the characterization of the different cell types involved in the synthesis of kynurenine metabolites and the underlying immunoregulatory mechanisms. With a focus on respiratory infections, the various attempts to characterize the kynurenine/tryptophan (K/T) ratio as an inflammatory marker are reviewed. Its implication in chronic lung inflammation and its exacerbation by respiratory pathogens is also discussed. The emergence of preclinical interventional studies targeting the kynurenine pathway opens the way for the future development of new therapies.

Keywords: COPD; Kynurenine; asthma; immunity; indoleamine 2 3-dioxygenase; lung; respiratory infection.

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Conflict of interest statement

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Schematic description of the kynurenine pathway. HAAO, 3-hydroxyanthranilate 3,4-dioxygenase; IDO, indoleamine 2,3-dioxygenase; KAT, kynurenine amino transferase; KMO, kynurenine monooxygenase; KYNU, Kynureninase; QPRT, quinolinate phosphoribosyltransferase; TDO, tryptophan dioxygenase.
Figure 2.
Figure 2.
Activation of the kynurenine pathway in the airways. During respiratory infection, fungi, bacteria or viruses induce IDO1 expression and enzymatic activity in epithelial, immune or even endothelial cells. Tryptophan is degraded to kynurenine metabolites, which modulate T-cell responses by downregulating Th1 and upregulating Th2 and Treg responses, and have antioxidant properties. Our hypothesis is that in chronic inflammatory conditions the IDO1 response is reduced and therefore the development of inflammation and oxidative stress is less controlled and may lead to exacerbations.
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