International Journal of Molecular Sciences

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Dear Colleagues,

Sphingosine 1-phosphate (S1P) is a well-defined bioactive lipid molecule derived from membrane sphingolipid metabolism. Sphingolipids represent the major lipid components on cellular membranes, mediating important biological functions for eukaryotic cells. The dynamic balance of sphingolipid levels is finely regulated by a variety of sphingolipid synthases, hydrolases, and metabolic enzymes. Dysfunction of some of these essential enzymes would directly break the balance, increasing susceptibility to various diseases. In this context, S1P is a kind of pleiotropic sphingophospholipid. S1P once transported out of the cell activates S1P1-5 receptors extracellularly modulating various pathological and physiological processes affecting the nervous systems, cardiovascular, immune, pulmonary, hepatic, and cancer-related risk. Hence, targeting S1P production, or blockade of its receptors might contribute to the development of novel therapeutic strategies to reduce metabolic and inflammatory alterations and diseases. At the same time, a better understanding of sphingolipid synthesis and degradation and how they are regulated by metabolic alterations holds great promise for the development of therapeutic targets and approaches.

For the Special Issue “The Role of Sphingosine-1-Phosphate in Human Metabolism and Disease”, we welcome your contributions in the form of original research and review articles on all aspects of sphingolipids especially Sphingosine-1-Phosphate and their role in physiological and pathophysiological metabolic processes.

Prof. Dr. Fiorentina Roviezzo
Guest Editor

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Keywords

sphingolipid signaling
sphingolipid metabolites
inflammation
metabolic diseases
lipolysis
glucose uptake
vasculature system
lung function
immune system

Published Papers (2 papers)

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Research

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16 pages, 3057 KiB

Open AccessArticle

HIV-1 Infection Results in Sphingosine-1-Phosphate Receptor 1 Dysregulation in the Human Thymus

by Rachel S. Resop, Bradley Salvatore, Shawn J. Kim, Brent R. Gordon, Bianca Blom, Dimitrios N. Vatakis and Christel H. Uittenbogaart

Int. J. Mol. Sci. 2023, 24(18), 13865; https://doi.org/10.3390/ijms241813865 - 8 Sep 2023

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Abstract

Regeneration of functional naïve T lymphocytes following the onset of human immunodeficiency virus (HIV) infection remains a crucial issue for people living with HIV (PLWH), even when adhering to antiretroviral therapy (ART). Thus far, reports on the impact of HIV-1 infection on the entry of thymic precursors and the egress of functional naïve T lymphocytes to and from the thymus are limited. We examined the impact of HIV-1 on Sphingosine-1-phosphate (S1P) signaling, which governs the egress of functional naïve thymocytes from the thymus to the periphery. Using in vitro experiments with primary human thymocytes and in vivo and ex vivo studies with humanized mice, we show that HIV-1 infection results in upregulation of the expression of S1P receptor 1 (S1PR1) in the human thymus. Intriguingly, this upregulation occurs during intrathymic infection (direct infection of the human thymic implant) as well as systemic infection in humanized mice. Moreover, considering the dysregulation of pro- and anti-inflammatory cytokines in infected thymi, the increased expression of S1PR1 in response to in vitro exposure to Interferon-Beta (IFN-β) and Tumor Necrosis Factor-Alpha (TNF-α) indicates that cytokine dysregulation following HIV infection may contribute to upregulation of S1PR1. Finally, an increased presence of CD3hiCD69− (fully mature) as well as CD3hiCD69+ (less mature) T cells in the spleen during HIV infection in humanized mice, combined with earlier expression of S1PR1 during thymocyte development, suggests that upregulation of S1PR1 may translate to increased or accelerated egress from the thymus. The egress of thymocytes that are not functionally mature from the thymus to peripheral blood and lymphoid organs may have implications for the immune function of PLWH. Full article

(This article belongs to the Special Issue The Role of Sphingosine-1-Phosphate in Human Metabolism and Disease)

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Review

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37 pages, 2253 KiB

Open AccessReview

Immune System and Brain/Intestinal Barrier Functions in Psychiatric Diseases: Is Sphingosine-1-Phosphate at the Helm?

by David Martín-Hernández, Marina Muñoz-López, Hiram Tendilla-Beltrán, Javier R. Caso, Borja García-Bueno, Luis Menchén and Juan C. Leza

Int. J. Mol. Sci. 2023, 24(16), 12634; https://doi.org/10.3390/ijms241612634 - 10 Aug 2023

Cited by 1 | Viewed by 2343

Abstract

Over the past few decades, extensive research has shed light on immune alterations and the significance of dysfunctional biological barriers in psychiatric disorders. The leaky gut phenomenon, intimately linked to the integrity of both brain and intestinal barriers, may play a crucial role in the origin of peripheral and central inflammation in these pathologies. Sphingosine-1-phosphate (S1P) is a bioactive lipid that regulates both the immune response and the permeability of biological barriers. Notably, S1P-based drugs, such as fingolimod and ozanimod, have received approval for treating multiple sclerosis, an autoimmune disease of the central nervous system (CNS), and ulcerative colitis, an inflammatory condition of the colon, respectively. Although the precise mechanisms of action are still under investigation, the effectiveness of S1P-based drugs in treating these pathologies sparks a debate on extending their use in psychiatry. This comprehensive review aims to delve into the molecular mechanisms through which S1P modulates the immune system and brain/intestinal barrier functions. Furthermore, it will specifically focus on psychiatric diseases, with the primary objective of uncovering the potential of innovative therapies based on S1P signaling. Full article

(This article belongs to the Special Issue The Role of Sphingosine-1-Phosphate in Human Metabolism and Disease)

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