PMID- 29021374
OWN - NLM
STAT- MEDLINE
DCOM- 20171120
LR  - 20181115
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Linking)
VI  - 199
IP  - 10
DP  - 2017 Nov 15
TI  - Reactive Oxygen Species Regulate the Inflammatory Function of NKT Cells through
      Promyelocytic Leukemia Zinc Finger.
PG  - 3478-3487
LID - 10.4049/jimmunol.1700567 [doi]
AB  - Reactive oxygen species (ROS) are byproducts of aerobic metabolism and contribute
      to both physiological and pathological conditions as second messengers. ROS are
      essential for activation of T cells, but how ROS influence NKT cells is unknown. 
      In the present study, we investigated the role of ROS in NKT cell function. We
      found that NKT cells, but not CD4 or CD8 T cells, have dramatically high ROS in
      the spleen and liver of mice but not in the thymus or adipose tissues.
      Accordingly, ROS-high NKT cells exhibited increased susceptibility and apoptotic 
      cell death with oxidative stress. High ROS in the peripheral NKT cells were
      primarily produced by NADPH oxidases and not mitochondria. We observed that
      sorted ROS-high NKT cells were enriched in NKT1 and NKT17 cells, whereas NKT2
      cells were dominant in ROS-low cells. Furthermore, treatment of NKT cells with
      antioxidants led to reduced frequencies of IFN-gamma- and IL-17-expressing cells,
      indicating that ROS play a role in regulating the inflammatory function of NKT
      cells. The transcription factor promyelocytic leukemia zinc finger (PLZF) seemed 
      to control the ROS levels. NKT cells from adipose tissues that do not express
      PLZF and those from PLZF haplodeficient mice have low ROS. Conversely, ROS were
      highly elevated in CD4 T cells from mice ectopically expressing PLZF. Thus, our
      findings demonstrate that PLZF controls ROS levels, which in turn governs the
      inflammatory function of NKT cells.
CI  - Copyright (c) 2017 by The American Association of Immunologists, Inc.
FAU - Kim, Yeung-Hyen
AU  - Kim YH
AUID- ORCID: 0000-0002-6171-6956
AD  - Department of Microbiology and Immunology, University of Michigan Medical School,
      Ann Arbor, MI 48109.
FAU - Kumar, Ajay
AU  - Kumar A
AD  - Department of Microbiology and Immunology, University of Michigan Medical School,
      Ann Arbor, MI 48109.
FAU - Chang, Cheong-Hee
AU  - Chang CH
AUID- ORCID: 0000-0001-8725-852X
AD  - Department of Microbiology and Immunology, University of Michigan Medical School,
      Ann Arbor, MI 48109.
FAU - Pyaram, Kalyani
AU  - Pyaram K
AD  - Department of Microbiology and Immunology, University of Michigan Medical School,
      Ann Arbor, MI 48109 kpyaram@umich.edu.
LA  - eng
GR  - P30 CA046592/CA/NCI NIH HHS/United States
GR  - R01 AI121156/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20171011
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Interleukin-17)
RN  - 0 (Promyelocytic Leukemia Zinc Finger Protein)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Zbtb16 protein, mouse)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 1.6.3.- (NADPH Oxidases)
SB  - AIM
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Cells, Cultured
MH  - Interferon-gamma/metabolism
MH  - Interleukin-17/metabolism
MH  - Liver/*immunology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - NADPH Oxidases/metabolism
MH  - Natural Killer T-Cells/*immunology
MH  - Oxidative Stress
MH  - Promyelocytic Leukemia Zinc Finger Protein/genetics/*metabolism
MH  - Reactive Oxygen Species/*metabolism
MH  - Spleen/*immunology
PMC - PMC5685185
MID - NIHMS907083
EDAT- 2017/10/13 06:00
MHDA- 2017/11/29 06:00
CRDT- 2017/10/13 06:00
PHST- 2017/04/21 00:00 [received]
PHST- 2017/09/14 00:00 [accepted]
PHST- 2017/10/13 06:00 [pubmed]
PHST- 2017/11/29 06:00 [medline]
PHST- 2017/10/13 06:00 [entrez]
AID - jimmunol.1700567 [pii]
AID - 10.4049/jimmunol.1700567 [doi]
PST - ppublish
SO  - J Immunol. 2017 Nov 15;199(10):3478-3487. doi: 10.4049/jimmunol.1700567. Epub
      2017 Oct 11.