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Int. J. Mol. Sci. 2018, 19(5), 1446; https://doi.org/10.3390/ijms19051446

Sphingosine-1-Phosphate Receptor 1 Is Involved in Non-Obese Diabetic Mouse Thymocyte Migration Disorders

1
Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, Brazil
2
National Institute of Science and Technology on Neuroimmunomodulation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, Brazil
3
Laboratory of Cell Biology, Institute of Biological and Health Sciences, Federal University of Alagoas, Maceió, Alagoas 57000-001, Brazil
4
Laboratory of Molecular Biology and Endemic Diseases, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, Brazil
5
French National Center for Scientific Research (CNRS), Mixed Research Unit (UMR) 8147, Paris Descartes University, 75006 Paris, France
*
Author to whom correspondence should be addressed.
Received: 2 February 2018 / Revised: 27 February 2018 / Accepted: 27 February 2018 / Published: 12 May 2018
(This article belongs to the Special Issue Sphingolipids: Signals and Disease)
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Abstract

NOD (non-obese diabetic) mice spontaneously develop type 1 diabetes following T cell-dependent destruction of pancreatic β cells. Several alterations are observed in the NOD thymus, including the presence of giant perivascular spaces (PVS) filled with single-positive (SP) CD4+ and CD8+ T cells that accumulate in the organ. These cells have a decreased expression of membrane CD49e (the α5 integrin chain of the fibronectin receptor VLA-5 (very late antigen-5). Herein, we observed lower sphingosine-1-phosphate receptor 1 (S1P1) expression in NOD mouse thymocytes when compared with controls, mainly in the mature SP CD4+CD62Lhi and CD8+CD62Lhi subpopulations bearing the CD49e phenotype. In contrast, differences in S1P1 expression were not observed in mature CD49e+ thymocytes. Functionally, NOD CD49e thymocytes had reduced S1P-driven migratory response, whereas CD49e+ cells were more responsive to S1P. We further noticed a decreased expression of the sphingosine-1-phosphate lyase (SGPL1) in NOD SP thymocytes, which can lead to a higher sphingosine-1-phosphate (S1P) expression around PVS and S1P1 internalization. In summary, our results indicate that the modulation of S1P1 expression and S1P/S1P1 interactions in NOD mouse thymocytes are part of the T-cell migratory disorder observed during the pathogenesis of type 1 diabetes. View Full-Text
Keywords: non-obese diabetic mice; thymus; sphingosine-1-phosphate; sphingosine-1-phosphate receptor 1; VLA-5 (very late antigen-5); cell migration non-obese diabetic mice; thymus; sphingosine-1-phosphate; sphingosine-1-phosphate receptor 1; VLA-5 (very late antigen-5); cell migration
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Lemos, J.P.; Smaniotto, S.; Messias, C.V.; Moreira, O.C.; Cotta-de-Almeida, V.; Dardenne, M.; Savino, W.; Mendes-da-Cruz, D.A. Sphingosine-1-Phosphate Receptor 1 Is Involved in Non-Obese Diabetic Mouse Thymocyte Migration Disorders. Int. J. Mol. Sci. 2018, 19, 1446.

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