@article{f95769b2c3ed4dc78fad8566d0fe4952,
title = "Critical Role for Very-Long Chain Sphingolipids in Invariant Natural Killer T Cell Development and Homeostasis",
abstract = "The role of sphingolipids (SLs) in the immune system has come under increasing scrutiny recently due to the emerging contributions that these important membrane components play in regulating a variety of immunological processes. The acyl chain length of SLs appears particularly critical in determining SL function. Here, we show a role for very-long acyl chain SLs (VLC-SLs) in invariant natural killer T (iNKT) cell maturation in the thymus and homeostasis in the liver. Ceramide synthase 2-null mice, which lack VLC-SLs, were susceptible to a hepatotropic strain of lymphocytic choriomeningitis virus, which is due to a reduction in the number of iNKT cells. Bone marrow chimera experiments indicated that hematopoietic-derived VLC-SLs are essential for maturation of iNKT cells in the thymus, whereas parenchymal-derived VLC-SLs are crucial for iNKT cell survival and maintenance in the liver. Our findings suggest a critical role for VLC-SL in iNKT cell physiology.",
author = "Ashish Saroha and Yael Pewzner-Jung and Ferreira, {Natalia S.} and Piyush Sharma and Youenn Jouan and Kelly, {Samuel L.} and Ester Feldmesser and Merrill, {Alfred H.} and Francois Trottein and Christophe Paget and Lang, {Karl S.} and Futerman, {Anthony H.}",
note = "The authors thank Dr. Tomer Meir Salame from the FACS unit in the Weizmann Institute of Science for his excellent technical support. The authors also thank the NIH Tetramer Core Facility, Emory University, Georgia, USA for providing CD1d-PBS57 loaded tetramers. This study was supported by the Atheroflux consortium (EU grant FP7-602222-2), the Israel Science Foundation (grant 1728/15), and the National Institutes of Health (grant GM076217). AS was supported by the Planning and Budgeting Committee program for outstanding post-doctoral researchers. AHF is the Joseph Meyerhoff Professor of Biochemistry at the Weizmann Institute of Science. AS and YP-J performed and designed the experiments and wrote the manuscript. NSF performed the RNA seq and EF did the bioinformatics analysis. PS analyzed viral titers. AM and SK carried out ESI–MS/MS analyses of SLs. YJ performed in vitro iNKT cell activation experiments, and FT and CP helped write the manuscript. KL provided the LCMV-WE virus, infected mice, and helped write the manuscript. AHF supervised and funded the studies and wrote the manuscript.",
year = "2017",
month = nov,
day = "1",
doi = "https://doi.org/10.3389/fimmu.2017.01386",
language = "الإنجليزيّة",
volume = "8",
journal = "Frontiers in Immunology",
issn = "1664-3224",
publisher = "Frontiers Media S.A.",
number = "NOV",
}