PMID- 29642281
OWN - NLM
STAT- MEDLINE
DCOM- 20190429
LR  - 20190429
IS  - 2050-4527 (Electronic)
IS  - 2050-4527 (Linking)
VI  - 6
IP  - 2
DP  - 2018 Jun
TI  - Fas Ligand localizes to intraluminal vesicles within NK cell cytolytic granules 
      and is enriched at the immune synapse.
PG  - 312-321
LID - 10.1002/iid3.219 [doi]
AB  - INTRODUCTION: T cell and NK cell cytotoxicity can be mediated via the 
      perforin/granzyme system and Fas Ligand (FasL, CD178). FasL is synthesized as a 
      type II transmembrane protein that binds its cognate receptor Fas (CD95). 
      Membrane-bound FasL is expressed on the plasma membrane of activated lymphocytes 
      and is the main form of FasL with cytotoxic activity, but whether FasL is 
      delivered to the immune synapse along with granzyme and perforin-containing 
      granules is unclear. METHODS: We stably expressed FasL-fluorescent fusion 
      proteins into human NK cells and examined the localization of FasL relative to 
      other intracellular markers by confocal and immunoelectron microscopy, and 
      examined the trafficking of FasL during formation of immune synapses with 
      HLA-deficient B cells. RESULTS: FasL co-localized with CD63 more strongly than 
      perforin or Lamp1+ in cytolytic granules. Electron microscopy revealed that FasL 
      is enriched on intraluminal vesicles (ILVs) adjacent to the dense-core within 
      cytolytic granules. In NK cells forming immune synapses with HLA-deficient B 
      cells, a portion of FasL-containing granules re-localize toward the immune 
      synapse, while a distinct pool of FasL remains at the distal pole of the cell. 
      CONCLUSIONS: Localization of FasL to intra-luminal vesicles within cytolytic 
      granules facilitates FasL trafficking to immune synapses and cytotoxic function 
      in NK cells.
CI  - (c) 2018 The Authors. Immunity, Inflammation and Disease Published by John Wiley & 
      Sons Ltd.
FAU - Lee, Jeansun
AU  - Lee J
AD  - CIMR, Department of Medicine, Cambridge University, Cambridge, UK.
AD  - Immunoregulation Section, Autoimmunity Branch, National Institutes of Arthritis 
      and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, 
      Maryland, USA.
FAU - Dieckmann, Nele M G
AU  - Dieckmann NMG
AD  - CIMR, Department of Medicine, Cambridge University, Cambridge, UK.
FAU - Edgar, James R
AU  - Edgar JR
AD  - CIMR, Department of Medicine, Cambridge University, Cambridge, UK.
FAU - Griffiths, Gillian M
AU  - Griffiths GM
AD  - CIMR, Department of Medicine, Cambridge University, Cambridge, UK.
FAU - Siegel, Richard M
AU  - Siegel RM
AUID- ORCID: 0000-0001-5953-9893
AD  - Immunoregulation Section, Autoimmunity Branch, National Institutes of Arthritis 
      and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, 
      Maryland, USA.
LA  - eng
GR  - Wellcome Trust/United Kingdom
GR  - 103930/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20180411
PL  - England
TA  - Immun Inflamm Dis
JT  - Immunity, inflammation and disease
JID - 101635460
RN  - 0 (CD63 protein, human)
RN  - 0 (FASLG protein, human)
RN  - 0 (Fas Ligand Protein)
RN  - 0 (HLA Antigens)
RN  - 0 (PRF1 protein, human)
RN  - 0 (Tetraspanin 30)
RN  - 126465-35-8 (Perforin)
RN  - EC 3.4.21.- (Granzymes)
SB  - IM
MH  - B-Lymphocytes/immunology/metabolism
MH  - Cell Culture Techniques
MH  - Cell Line
MH  - Cytoplasmic Granules/immunology/*metabolism/ultrastructure
MH  - Fas Ligand Protein/immunology/*metabolism/ultrastructure
MH  - Granzymes/metabolism
MH  - HLA Antigens/metabolism
MH  - Humans
MH  - Immunological Synapses/immunology/*metabolism/ultrastructure
MH  - Killer Cells, Natural/cytology/immunology/*metabolism/ultrastructure
MH  - Microscopy, Electron
MH  - Perforin/metabolism
MH  - Tetraspanin 30/immunology/metabolism
PMC - PMC5946154
OTO - NOTNLM
OT  - Cytolytic granules
OT  - fas ligand (CD178)
OT  - immune synapse
OT  - intra-luminal vesicles (ILVs)
EDAT- 2018/04/12 06:00
MHDA- 2019/04/30 06:00
PMCR- 2018/04/11
CRDT- 2018/04/12 06:00
PHST- 2016/11/23 00:00 [received]
PHST- 2018/01/16 00:00 [revised]
PHST- 2018/02/06 00:00 [accepted]
PHST- 2018/04/12 06:00 [pubmed]
PHST- 2019/04/30 06:00 [medline]
PHST- 2018/04/12 06:00 [entrez]
PHST- 2018/04/11 00:00 [pmc-release]
AID - IID3219 [pii]
AID - 10.1002/iid3.219 [doi]
PST - ppublish
SO  - Immun Inflamm Dis. 2018 Jun;6(2):312-321. doi: 10.1002/iid3.219. Epub 2018 Apr 
      11.