Circadian control of kynurenine pathway enzymes in the rat pineal gland, liver, and heart and tissue- and enzyme-specific responses to lipopolysaccharide

Moravcová, Simona; Spišská, Veronika; Pačesová, Dominika; Hrubcová, Leona; Kubištová, Aneta; Novotný, Jiřı́; Bendová, Zdeňka

doi:10.1016/j.abb.2022.109213

Cited by 6 publications

(1 citation statement)

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“…Although the relevance of Trp catabolic pathways in both the regulation of immune functions against infections and in sleep and circadian physiology is widely accepted, a direct connection between the circadian system and the Kyn pathway in peripheral tissues has remained elusive. An oscillatory expression of some Kyn pathway enzymes has been documented in rat pineal gland ( 30 ). Furthermore, a very recent work has demonstrated how Trp metabolites regulate physiological circadian rhythms in both the liver and the SCN ( 31 ).…”

Section: Discussionmentioning

confidence: 99%

The circadian control of tryptophan metabolism regulates the host response to pulmonary fungal infections

et al. 2023

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The environmental light/dark cycle has left its mark on the body’s physiological functions to condition not only our inner biology, but also the interaction with external cues. In this scenario, the circadian regulation of the immune response has emerged as a critical factor in defining the host-pathogen interaction and the identification of the underlying circuitry represents a prerequisite for the development of circadian-based therapeutic strategies. The possibility to track down the circadian regulation of the immune response to a metabolic pathway would represent a unique opportunity in this direction. Herein, we show that the metabolism of the essential amino acid tryptophan, involved in the regulation of fundamental processes in mammals, is regulated in a circadian manner in both murine and human cells and in mouse tissues. By resorting to a murine model of pulmonary infection with the opportunistic fungus Aspergillus fumigatus, we showed that the circadian oscillation in the lung of the tryptophan-degrading enzyme indoleamine 2,3-dioxygenase (IDO)1, generating the immunoregulatory kynurenine, resulted in diurnal changes in the immune response and the outcome of fungal infection. In addition, the circadian regulation of IDO1 drives such diurnal changes in a preclinical model of cystic fibrosis, an autosomal recessive disease characterized by progressive lung function decline and recurrent infections, thus acquiring considerable clinical relevance. Our results demonstrate that the circadian rhythm at the intersection between metabolism and immune response underlies the diurnal changes in host-fungal interaction, thus paving the way for a circadian-based antimicrobial therapy.

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Section: Discussionmentioning

confidence: 99%