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Targeting the Dopaminergic System in Autoimmunity

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Abstract

Dopamine has emerged as a fundamental regulator of inflammation. In this regard, it has been shown that dopaminergic signalling pathways are key players promoting homeostasis between the central nervous system and the immune system. Dysregulation in the dopaminergic system affects both innate and adaptive immunity, contributing to the development of numerous autoimmune and inflammatory pathologies. This makes dopamine receptors interesting therapeutic targets for either the development of new treatments or repurposing of already available pharmacological drugs. Dopamine receptors are broadly expressed on different immune cells with multifunctional effects depending on the dopamine concentration available and the pattern of expression of five dopamine receptors displaying different affinities for dopamine. Thus, impaired dopaminergic signalling through different dopamine receptors may result in altered behaviour of immunity, contributing to the development and progression of autoimmune pathologies. In this review we discuss the current evidence involving the dopaminergic system in inflammatory bowel disease, multiple sclerosis and Parkinson’s disease. In addition, we summarise and analyse the therapeutic approaches designed to attenuate disease development and progression by targeting the dopaminergic system.

Targetting the dopaminergic system in autoimmunity.

Effector T-cells (Teff) orchestrate inflamamtion involved in autoimmunity, whilst regulatory T-cells (Tregs) suppress Teff activity promoting tolerance to self-constituents. Dopamine has emerged as a key regulator of Teff and Tregs function, thereby dopamine receptors have becoming important therapeutic targets in autoimmune disorders, especially in those affecting the brain and the gut, where dopamine levels strongly change with inflammation.

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Acknowledgements

This work was supported by Programa de Apoyo a Centros con Financiamiento Basal AFB-170004 (to Fundación Ciencia & Vida) from “Comisión Nacional de Investigación Científica y Tecnológica de Chile (CONICYT)” and by grants FONDECYT-1170093 (to R.P.) from “Fondo Nacional de Desarrollo Científico y Tecnológico de Chile”, and MJFF-10332.01 (to R.P.) and MJFF-15076 (to R.P.) from Michael J. Fox Foundation for Parkinson Research. PV is supported by “Progama PostDoc Hinge” from Fundación Ciencia & Vida.

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  1. Laboratorio de Neuroinmunología, Fundación Ciencia & Vida, Av. Zañartu 1482, Ñuñoa, 7780272, Santiago, Chile

    Pia M. Vidal & Rodrigo Pacheco

  2. Departamento de Ciencias Biológicas, Facultad de Ciencias de la Vida, Universidad Andres Bello, 8370146, Santiago, Chile

    Rodrigo Pacheco

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Vidal, P.M., Pacheco, R. Targeting the Dopaminergic System in Autoimmunity. J Neuroimmune Pharmacol 15, 57–73 (2020). https://doi.org/10.1007/s11481-019-09834-5

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