Signaling through the S1P−S1PR Axis in the Gut, the Immune and the Central Nervous System in Multiple Sclerosis: Implication for Pathogenesis and Treatment

Sphingosine 1-phosphate (S1P) is a signaling molecule with complex biological functions that are exerted through the activation of sphingosine 1-phosphate receptors 1–5 (S1PR1–5). S1PR expression is necessary for cell proliferation, angiogenesis, neurogenesis and, importantly, for the egress of lymp...

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Autores principales:	Simela Chatzikonstantinou, Vasiliki Poulidou, Marianthi Arnaoutoglou, Dimitrios Kazis, Ioannis Heliopoulos, Nikolaos Grigoriadis, Marina Boziki
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	sphingosine 1-phoshate sphingosine 1-phosphate receptors multiple sclerosis gut–brain axis gut microbiota fingolimod Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/1b0c7d85cb8f43609f39a7f1b9a5c267
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spelling	oai:doaj.org-article:1b0c7d85cb8f43609f39a7f1b9a5c2672021-11-25T17:12:59ZSignaling through the S1P−S1PR Axis in the Gut, the Immune and the Central Nervous System in Multiple Sclerosis: Implication for Pathogenesis and Treatment10.3390/cells101132172073-4409https://doaj.org/article/1b0c7d85cb8f43609f39a7f1b9a5c2672021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/3217https://doaj.org/toc/2073-4409Sphingosine 1-phosphate (S1P) is a signaling molecule with complex biological functions that are exerted through the activation of sphingosine 1-phosphate receptors 1–5 (S1PR1–5). S1PR expression is necessary for cell proliferation, angiogenesis, neurogenesis and, importantly, for the egress of lymphocytes from secondary lymphoid organs. Since the inflammatory process is a key element of immune-mediated diseases, including multiple sclerosis (MS), S1PR modulators are currently used to ameliorate systemic immune responses. The ubiquitous expression of S1PRs by immune, intestinal and neural cells has significant implications for the regulation of the gut–brain axis. The dysfunction of this bidirectional communication system may be a significant factor contributing to MS pathogenesis, since an impaired intestinal barrier could lead to interaction between immune cells and microbiota with a potential to initiate abnormal local and systemic immune responses towards the central nervous system (CNS). It appears that the secondary mechanisms of S1PR modulators affecting the gut immune system, the intestinal barrier and directly the CNS, are coordinated to promote therapeutic effects. The scope of this review is to focus on S1P−S1PR functions in the cells of the CNS, the gut and the immune system with particular emphasis on the immunologic effects of S1PR modulation and its implication in MS.Simela ChatzikonstantinouVasiliki PoulidouMarianthi ArnaoutoglouDimitrios KazisIoannis HeliopoulosNikolaos GrigoriadisMarina BozikiMDPI AGarticlesphingosine 1-phoshatesphingosine 1-phosphate receptorsmultiple sclerosisgut–brain axisgut microbiotafingolimodBiology (General)QH301-705.5ENCells, Vol 10, Iss 3217, p 3217 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	sphingosine 1-phoshate sphingosine 1-phosphate receptors multiple sclerosis gut–brain axis gut microbiota fingolimod Biology (General) QH301-705.5
spellingShingle	sphingosine 1-phoshate sphingosine 1-phosphate receptors multiple sclerosis gut–brain axis gut microbiota fingolimod Biology (General) QH301-705.5 Simela Chatzikonstantinou Vasiliki Poulidou Marianthi Arnaoutoglou Dimitrios Kazis Ioannis Heliopoulos Nikolaos Grigoriadis Marina Boziki Signaling through the S1P−S1PR Axis in the Gut, the Immune and the Central Nervous System in Multiple Sclerosis: Implication for Pathogenesis and Treatment
description	Sphingosine 1-phosphate (S1P) is a signaling molecule with complex biological functions that are exerted through the activation of sphingosine 1-phosphate receptors 1–5 (S1PR1–5). S1PR expression is necessary for cell proliferation, angiogenesis, neurogenesis and, importantly, for the egress of lymphocytes from secondary lymphoid organs. Since the inflammatory process is a key element of immune-mediated diseases, including multiple sclerosis (MS), S1PR modulators are currently used to ameliorate systemic immune responses. The ubiquitous expression of S1PRs by immune, intestinal and neural cells has significant implications for the regulation of the gut–brain axis. The dysfunction of this bidirectional communication system may be a significant factor contributing to MS pathogenesis, since an impaired intestinal barrier could lead to interaction between immune cells and microbiota with a potential to initiate abnormal local and systemic immune responses towards the central nervous system (CNS). It appears that the secondary mechanisms of S1PR modulators affecting the gut immune system, the intestinal barrier and directly the CNS, are coordinated to promote therapeutic effects. The scope of this review is to focus on S1P−S1PR functions in the cells of the CNS, the gut and the immune system with particular emphasis on the immunologic effects of S1PR modulation and its implication in MS.
format	article
author	Simela Chatzikonstantinou Vasiliki Poulidou Marianthi Arnaoutoglou Dimitrios Kazis Ioannis Heliopoulos Nikolaos Grigoriadis Marina Boziki
author_facet	Simela Chatzikonstantinou Vasiliki Poulidou Marianthi Arnaoutoglou Dimitrios Kazis Ioannis Heliopoulos Nikolaos Grigoriadis Marina Boziki
author_sort	Simela Chatzikonstantinou
title	Signaling through the S1P−S1PR Axis in the Gut, the Immune and the Central Nervous System in Multiple Sclerosis: Implication for Pathogenesis and Treatment
title_short	Signaling through the S1P−S1PR Axis in the Gut, the Immune and the Central Nervous System in Multiple Sclerosis: Implication for Pathogenesis and Treatment
title_full	Signaling through the S1P−S1PR Axis in the Gut, the Immune and the Central Nervous System in Multiple Sclerosis: Implication for Pathogenesis and Treatment
title_fullStr	Signaling through the S1P−S1PR Axis in the Gut, the Immune and the Central Nervous System in Multiple Sclerosis: Implication for Pathogenesis and Treatment
title_full_unstemmed	Signaling through the S1P−S1PR Axis in the Gut, the Immune and the Central Nervous System in Multiple Sclerosis: Implication for Pathogenesis and Treatment
title_sort	signaling through the s1p−s1pr axis in the gut, the immune and the central nervous system in multiple sclerosis: implication for pathogenesis and treatment
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/1b0c7d85cb8f43609f39a7f1b9a5c267
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Signaling through the S1P−S1PR Axis in the Gut, the Immune and the Central Nervous System in Multiple Sclerosis: Implication for Pathogenesis and Treatment

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