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Sphingosine-1-phosphate receptor-1 (S1P(1)) is expressed by lymphocytes, dendritic cells, and endothelium and modulated during inflammatory bowel disease

The sphingosine-1-phosphate receptor-1 (S1P(1)) agonist ozanimod ameliorates ulcerative colitis, yet its mechanism of action is unknown. Here we examine the cell subsets that express S1P(1) in intestine using S1P(1)-eGFP mice, the regulation of S1P(1) expression in lymphocytes after administration o...

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Autores principales: Karuppuchamy, Thangaraj, Behrens, En-hui, González-Cabrera, Pedro, Sarkisyan, Gor, Gima, Lauren, Boyer, Joshua D., Bamias, Giorgos, Jedlicka, Paul, Veny, Marisol, Clark, David, Peach, Robert, Scott, Fiona, Rosen, Hugh, Rivera-Nieves, Jesús
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5053832/
https://www.ncbi.nlm.nih.gov/pubmed/27049060
http://dx.doi.org/10.1038/mi.2016.35
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author Karuppuchamy, Thangaraj
Behrens, En-hui
González-Cabrera, Pedro
Sarkisyan, Gor
Gima, Lauren
Boyer, Joshua D.
Bamias, Giorgos
Jedlicka, Paul
Veny, Marisol
Clark, David
Peach, Robert
Scott, Fiona
Rosen, Hugh
Rivera-Nieves, Jesús
author_facet Karuppuchamy, Thangaraj
Behrens, En-hui
González-Cabrera, Pedro
Sarkisyan, Gor
Gima, Lauren
Boyer, Joshua D.
Bamias, Giorgos
Jedlicka, Paul
Veny, Marisol
Clark, David
Peach, Robert
Scott, Fiona
Rosen, Hugh
Rivera-Nieves, Jesús
author_sort Karuppuchamy, Thangaraj
collection PubMed
description The sphingosine-1-phosphate receptor-1 (S1P(1)) agonist ozanimod ameliorates ulcerative colitis, yet its mechanism of action is unknown. Here we examine the cell subsets that express S1P(1) in intestine using S1P(1)-eGFP mice, the regulation of S1P(1) expression in lymphocytes after administration of DSS, after colitis induced by transfer of CD4(+)CD45RB(hi) cells and by crossing a mouse with TNF-driven ileitis with S1P(1)-eGFP mice. We then assayed the expression of enzymes that regulate intestinal S1P levels, and the effect of FTY720 on lymphocyte behavior and S1P(1) expression. We found that not only T and B cells express S1P(1), but also dendritic (DC) and endothelial cells. Furthermore, chronic but not acute inflammatory signals increased S1P(1) expression, while the enzymes that control tissue S1P levels in mice and humans with IBD were uniformly dysregulated, favoring synthesis over degradation. Finally, we observed that FTY720 reduced T cell velocity and induced S1P(1) degradation and retention of naïve but not effector T cells. Our data demonstrate that chronic inflammation modulates S1P(1) expression and tissue S1P levels and suggests that the anti-inflammatory properties of S1PR agonists might not be solely due to their lymphopenic effects, but also due to potential effects on DC migration and vascular barrier function.
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spelling pubmed-50538322017-02-01 Sphingosine-1-phosphate receptor-1 (S1P(1)) is expressed by lymphocytes, dendritic cells, and endothelium and modulated during inflammatory bowel disease Karuppuchamy, Thangaraj Behrens, En-hui González-Cabrera, Pedro Sarkisyan, Gor Gima, Lauren Boyer, Joshua D. Bamias, Giorgos Jedlicka, Paul Veny, Marisol Clark, David Peach, Robert Scott, Fiona Rosen, Hugh Rivera-Nieves, Jesús Mucosal Immunol Article The sphingosine-1-phosphate receptor-1 (S1P(1)) agonist ozanimod ameliorates ulcerative colitis, yet its mechanism of action is unknown. Here we examine the cell subsets that express S1P(1) in intestine using S1P(1)-eGFP mice, the regulation of S1P(1) expression in lymphocytes after administration of DSS, after colitis induced by transfer of CD4(+)CD45RB(hi) cells and by crossing a mouse with TNF-driven ileitis with S1P(1)-eGFP mice. We then assayed the expression of enzymes that regulate intestinal S1P levels, and the effect of FTY720 on lymphocyte behavior and S1P(1) expression. We found that not only T and B cells express S1P(1), but also dendritic (DC) and endothelial cells. Furthermore, chronic but not acute inflammatory signals increased S1P(1) expression, while the enzymes that control tissue S1P levels in mice and humans with IBD were uniformly dysregulated, favoring synthesis over degradation. Finally, we observed that FTY720 reduced T cell velocity and induced S1P(1) degradation and retention of naïve but not effector T cells. Our data demonstrate that chronic inflammation modulates S1P(1) expression and tissue S1P levels and suggests that the anti-inflammatory properties of S1PR agonists might not be solely due to their lymphopenic effects, but also due to potential effects on DC migration and vascular barrier function. 2016-04-06 2017-01 /pmc/articles/PMC5053832/ /pubmed/27049060 http://dx.doi.org/10.1038/mi.2016.35 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Karuppuchamy, Thangaraj
Behrens, En-hui
González-Cabrera, Pedro
Sarkisyan, Gor
Gima, Lauren
Boyer, Joshua D.
Bamias, Giorgos
Jedlicka, Paul
Veny, Marisol
Clark, David
Peach, Robert
Scott, Fiona
Rosen, Hugh
Rivera-Nieves, Jesús
Sphingosine-1-phosphate receptor-1 (S1P(1)) is expressed by lymphocytes, dendritic cells, and endothelium and modulated during inflammatory bowel disease
title Sphingosine-1-phosphate receptor-1 (S1P(1)) is expressed by lymphocytes, dendritic cells, and endothelium and modulated during inflammatory bowel disease
title_full Sphingosine-1-phosphate receptor-1 (S1P(1)) is expressed by lymphocytes, dendritic cells, and endothelium and modulated during inflammatory bowel disease
title_fullStr Sphingosine-1-phosphate receptor-1 (S1P(1)) is expressed by lymphocytes, dendritic cells, and endothelium and modulated during inflammatory bowel disease
title_full_unstemmed Sphingosine-1-phosphate receptor-1 (S1P(1)) is expressed by lymphocytes, dendritic cells, and endothelium and modulated during inflammatory bowel disease
title_short Sphingosine-1-phosphate receptor-1 (S1P(1)) is expressed by lymphocytes, dendritic cells, and endothelium and modulated during inflammatory bowel disease
title_sort sphingosine-1-phosphate receptor-1 (s1p(1)) is expressed by lymphocytes, dendritic cells, and endothelium and modulated during inflammatory bowel disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5053832/
https://www.ncbi.nlm.nih.gov/pubmed/27049060
http://dx.doi.org/10.1038/mi.2016.35
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