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Publication : Syndecan-1 identifies and controls the frequency of IL-17-producing naïve natural killer T (NKT17) cells in mice.

First Author  Dai H Year  2015
Journal  Eur J Immunol Volume  45
Issue  11 Pages  3045-51
PubMed ID  26300525 Mgi Jnum  J:233382
Mgi Id  MGI:5784574 Doi  10.1002/eji.201545532
Citation  Dai H, et al. (2015) Syndecan-1 identifies and controls the frequency of IL-17-producing naive natural killer T (NKT17) cells in mice. Eur J Immunol 45(11):3045-51
abstractText  Invariant natural killer T (iNKT) cells recognize glycolipids as antigens and diversify into NKT1 (IFN-gamma), NKT2 (IL-4), and NKT17 (IL-17) functional subsets while developing in the thymus. Mechanisms that govern the balance between these functional subsets are poorly understood due, partly, to the lack of distinguishing surface markers. Here we identify the heparan sulfate proteoglycan syndecan-1 (sdc1) as a specific marker of naive thymic NKT17 cells in mice and show that sdc1 deficiency significantly increases thymic NKT17 cells at the expense of NKT1 cells, leading to impaired iNKT cell-derived IFN-gamma, both in vitro and in vivo. Using surface expression of sdc1 to identify NKT17 cells, we confirm differential tissue localization and interstrain variability of NKT17 cells, and reveal that NKT17 cells express high levels of TCR-beta, preferentially use Vbeta8, and are more highly sensitive to a-GalCer than to CD3/CD28 stimulation. These findings provide a novel, noninvasive, simple method for identification, and viable sorting of naive NKT17 cells from unmanipulated mice, and suggest that sdc1 expression negatively regulates homeostasis in iNKT cells. In addition, these findings lay the groundwork for investigating the mechanisms by which sdc1 regulates NKT17 cells.
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