PMID- 31629012
OWN - NLM
STAT- MEDLINE
DCOM- 20200519
LR  - 20200519
IS  - 1879-3185 (Electronic)
IS  - 0300-483X (Linking)
VI  - 428
DP  - 2019 Dec 1
TI  - Attenuated cholesterol metabolism pathway suppresses regulatory T cell 
      development in prenatal nicotine exposed female mice.
PG  - 152309
LID - S0300-483X(19)30266-5 [pii]
LID - 10.1016/j.tox.2019.152309 [doi]
AB  - The recession of regulatory T cells (Tregs) contributes to development of 
      autoimmune disease. Our previous study suggested that prenatal nicotine exposure 
      (PNE) inhibited Tregs frequency in offspring, but the mechanisms are still 
      uncertain. This study aimed to explore the molecular mechanisms of PNE-induced 
      Tregs inhibition from the perspective of cellular cholesterol homeostasis both in 
      vivo and in vitro. PNE mice model were established by 3 mg/kg/d nicotine 
      administration in Balb/c strain from gestational day (GD) 9 to GD 18. The results 
      showed that PNE significantly decreased thymic Tregs frequency in neonatal 
      offspring. The activation of mTOR and downregulation of p-STAT5/Foxp3 pathway of 
      Tregs were observed in PNE offspring. Mechanism study found that PNE elevated 
      ATP-binding cassette transporter G1 (ABCG1) expression and decreased 
      intracellular cholesterol content of Tregs in offspring, indicating impaired 
      intracellular cholesterol homeostasis. Similar results were observed in 
      1 muM nicotine-treated primary thymocytes in vitro. Further, 
      cholesterol-replenishment can abrogate nicotine-induced mTOR activation and the 
      following suppression of p-STAT5/Foxp3 pathway and Tregs frequency. In addition, 
      Abcg1 siRNA transfection can partly reverse the nicotine-decreased intracellular 
      cholesterol content and cell frequency of Tregs. In conclusion, this study showed 
      that PNE could suppress Tregs development in female mice by up-regulating 
      ABCG1-dependent cholesterol efflux, and suggested that PNE-induced thymic Tregs 
      recession of offspring at early life was the developmental origin mechanism of 
      immune dysfunction in later life.
CI  - Copyright (c) 2019 Elsevier B.V. All rights reserved.
FAU - Wen, Xiao
AU  - Wen X
AD  - Department of Pharmacology, Wuhan University School of Basic Medical Sciences, 
      Wuhan 430071, China.
FAU - Zhao, Wen-Hao
AU  - Zhao WH
AD  - Department of Pharmacology, Wuhan University School of Basic Medical Sciences, 
      Wuhan 430071, China.
FAU - Chen, Lan-Zhou
AU  - Chen LZ
AD  - Hubei Key Laboratory of Biomass-Resources Chemistry and Environmental 
      Biotechnology, Wuhan University School of Resource and Environmental Sciences, 
      Wuhan, 430079, China.
FAU - Qu, Wen
AU  - Qu W
AD  - Department of Pharmacology, Wuhan University School of Basic Medical Sciences, 
      Wuhan 430071, China.
FAU - Liu, Han-Xiao
AU  - Liu HX
AD  - Department of Pharmacology, Wuhan University School of Basic Medical Sciences, 
      Wuhan 430071, China.
FAU - Yan, Hui-Yi
AU  - Yan HY
AD  - Department of Pharmacology, Wuhan University School of Basic Medical Sciences, 
      Wuhan 430071, China.
FAU - Hou, Li-Fang
AU  - Hou LF
AD  - Department of Pharmacology, Wuhan University School of Basic Medical Sciences, 
      Wuhan 430071, China.
FAU - Ping, Jie
AU  - Ping J
AD  - Department of Pharmacology, Wuhan University School of Basic Medical Sciences, 
      Wuhan 430071, China. Electronic address: pingjie@whu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20191016
PL  - Ireland
TA  - Toxicology
JT  - Toxicology
JID - 0361055
RN  - 6M3C89ZY6R (Nicotine)
RN  - 97C5T2UQ7J (Cholesterol)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Cholesterol/*metabolism
MH  - Female
MH  - Male
MH  - Maternal-Fetal Exchange
MH  - Mice, Inbred BALB C
MH  - Nicotine/*toxicity
MH  - Pregnancy
MH  - *Prenatal Exposure Delayed Effects
MH  - T-Lymphocytes, Regulatory/*drug effects
MH  - Thymus Gland/cytology
OTO - NOTNLM
OT  - ATP-binding cassette transporter
OT  - Cholesterol efflux
OT  - Prenatal nicotine exposure
OT  - Regulatory T cells
EDAT- 2019/10/20 06:00
MHDA- 2020/05/20 06:00
CRDT- 2019/10/20 06:00
PHST- 2019/06/12 00:00 [received]
PHST- 2019/10/10 00:00 [revised]
PHST- 2019/10/15 00:00 [accepted]
PHST- 2019/10/20 06:00 [pubmed]
PHST- 2020/05/20 06:00 [medline]
PHST- 2019/10/20 06:00 [entrez]
AID - S0300-483X(19)30266-5 [pii]
AID - 10.1016/j.tox.2019.152309 [doi]
PST - ppublish
SO  - Toxicology. 2019 Dec 1;428:152309. doi: 10.1016/j.tox.2019.152309. Epub 2019 Oct 
      16.