Tryptophan metabolism as a ‘reflex’ feature of neuroimmune communication: Sensor and effector functions for the indoleamine‐2, 3‐dioxygenase kynurenine pathway

The kynurenine pathway functions as a stress-protection reflex circuit. Indoleamine-2-3-dioxygenase (IDO) is induced by ‘Physical Stressors’ such as infection or tissue damage; tryptophan-2,3-dioxygenase (TDO) is activated by psychological pressures via glucocorticosteroids, or elevated dietary tryptophan. These initiate a co-ordinated whole-body reflex, with kynurenine metabolites as the effectors. Kynurenic aci d regulates CNS excitability via glutamate blockade or GPR35 activation and modulates immunological activity by inhibiting TNF and promoting tolerance. Quinolinic acid increases CNS excitability, oxidative stress and chemokine production. The kynurenate–quinolinate balance compensates for over- or under-activity in the CNS or immune systems. AbstractAlthough the central nervous system (CNS) and immune system were regarded as independent entities, it is now clear that immune system cells can influence the CNS, and neuroglial activity influences the immune system. Despite the many clinical implications for this ‘neuroimmune interface’, its detailed operation at the molecular level remains unclear. This narrative review focuses on the metabolism of tryptophan along the kynurenine pathway, since its products have critical actions in both the nervous and immune systems, placing it in a unique position to influence neuroimmune communication. In particular, since the kynurenine pathway is activated by pro-inflammatory mediators, it is proposed that physical and ps...
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: REVIEW Source Type: research