AUTHOR=Saroha Ashish , Pewzner-Jung Yael , Ferreira Natalia S. , Sharma Piyush , Jouan Youenn , Kelly Samuel L. , Feldmesser Ester , Merrill Alfred H. , Trottein François , Paget Christophe , Lang Karl S. , Futerman Anthony H. 

TITLE=Critical Role for Very-Long Chain Sphingolipids in Invariant Natural Killer T Cell Development and Homeostasis

JOURNAL=Frontiers in Immunology

VOLUME=8

YEAR=2017

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2017.01386

DOI=10.3389/fimmu.2017.01386

ISSN=1664-3224

ABSTRACT=<p>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 (<italic>i</italic>NKT) 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 <italic>i</italic>NKT cells. Bone marrow chimera experiments indicated that hematopoietic-derived VLC-SLs are essential for maturation of <italic>i</italic>NKT cells in the thymus, whereas parenchymal-derived VLC-SLs are crucial for <italic>i</italic>NKT cell survival and maintenance in the liver. Our findings suggest a critical role for VLC-SL in <italic>i</italic>NKT cell physiology.</p>