PMID- 27482882
OWN - NLM
STAT- MEDLINE
DCOM- 20170926
LR  - 20220129
IS  - 1558-8238 (Electronic)
IS  - 0021-9738 (Print)
IS  - 0021-9738 (Linking)
VI  - 126
IP  - 9
DP  - 2016 Sep 1
TI  - Loss of ABCG1 influences regulatory T cell differentiation and atherosclerosis.
PG  - 3236-46
LID - 83136 [pii]
LID - 10.1172/JCI83136 [doi]
AB  - ATP-binding cassette transporter G1 (ABCG1) promotes cholesterol accumulation and 
      alters T cell homeostasis, which may contribute to progression of 
      atherosclerosis. Here, we investigated how the selective loss of ABCG1 in T cells 
      impacts atherosclerosis in LDL receptor-deficient (LDLR-deficient) mice, a model 
      of the disease. In LDLR-deficient mice fed a high-cholesterol diet, T 
      cell-specific ABCG1 deficiency protected against atherosclerotic lesions. 
      Furthermore, T cell-specific ABCG1 deficiency led to a 30% increase in Treg 
      percentages in aorta and aorta-draining lymph nodes (LNs) of these mice compared 
      with animals with only LDLR deficiency. When Abcg1 was selectively deleted in 
      Tregs of LDLR-deficient mice, we observed a 30% increase in Treg percentages in 
      aorta and aorta-draining LNs and reduced atherosclerosis. In the absence of 
      ABCG1, intracellular cholesterol accumulation led to downregulation of the mTOR 
      pathway, which increased the differentiation of naive CD4 T cells into Tregs. The 
      increase in Tregs resulted in reduced T cell activation and increased IL-10 
      production by T cells. Last, we found that higher ABCG1 expression in Tregs was 
      associated with a higher frequency of these cells in human blood samples. Our 
      study indicates that ABCG1 regulates T cell differentiation into Tregs, 
      highlighting a pathway by which cholesterol accumulation can influence T cell 
      homeostasis in atherosclerosis.
FAU - Cheng, Hsin-Yuan
AU  - Cheng HY
FAU - Gaddis, Dalia E
AU  - Gaddis DE
FAU - Wu, Runpei
AU  - Wu R
FAU - McSkimming, Chantel
AU  - McSkimming C
FAU - Haynes, LaTeira D
AU  - Haynes LD
FAU - Taylor, Angela M
AU  - Taylor AM
FAU - McNamara, Coleen A
AU  - McNamara CA
FAU - Sorci-Thomas, Mary
AU  - Sorci-Thomas M
FAU - Hedrick, Catherine C
AU  - Hedrick CC
LA  - eng
GR  - R01 HL127649/HL/NHLBI NIH HHS/United States
GR  - 13POST14660055/AHA_/American Heart Association-American Stroke Association/United 
      States
GR  - P01 HL055798/HL/NHLBI NIH HHS/United States
GR  - F31 HL110668/HL/NHLBI NIH HHS/United States
GR  - R01 HL112276/HL/NHLBI NIH HHS/United States
PT  - Journal Article
DEP - 20160802
PL  - United States
TA  - J Clin Invest
JT  - The Journal of clinical investigation
JID - 7802877
RN  - 0 (ABCG1 protein, human)
RN  - 0 (ABCG1 protein, mouse)
RN  - 0 (ATP Binding Cassette Transporter, Subfamily G, Member 1)
RN  - 0 (Forkhead Transcription Factors)
RN  - 0 (Foxp3 protein, mouse)
RN  - 0 (Lipoproteins)
RN  - 0 (Receptors, LDL)
RN  - 126880-86-2 (L-Selectin)
RN  - 130068-27-8 (Interleukin-10)
RN  - 97C5T2UQ7J (Cholesterol)
SB  - IM
MH  - ATP Binding Cassette Transporter, Subfamily G, Member 1/genetics/*metabolism
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Animals
MH  - Aorta/metabolism
MH  - Atherosclerosis/*metabolism
MH  - CD4-Positive T-Lymphocytes/*cytology
MH  - Cell Differentiation
MH  - Cell Proliferation
MH  - Cholesterol/metabolism
MH  - Disease Progression
MH  - Female
MH  - Forkhead Transcription Factors/metabolism
MH  - Humans
MH  - Interleukin-10/metabolism
MH  - L-Selectin/metabolism
MH  - Lipoproteins/blood
MH  - Lymph Nodes/pathology
MH  - Male
MH  - Membrane Microdomains
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Middle Aged
MH  - Phenotype
MH  - Receptors, LDL/genetics
MH  - Signal Transduction
MH  - T-Lymphocytes, Regulatory/cytology
PMC - PMC5004951
EDAT- 2016/08/03 06:00
MHDA- 2017/09/28 06:00
PMCR- 2016/12/01
CRDT- 2016/08/03 06:00
PHST- 2015/06/05 00:00 [received]
PHST- 2016/06/02 00:00 [accepted]
PHST- 2016/08/03 06:00 [entrez]
PHST- 2016/08/03 06:00 [pubmed]
PHST- 2017/09/28 06:00 [medline]
PHST- 2016/12/01 00:00 [pmc-release]
AID - 83136 [pii]
AID - 10.1172/JCI83136 [doi]
PST - ppublish
SO  - J Clin Invest. 2016 Sep 1;126(9):3236-46. doi: 10.1172/JCI83136. Epub 2016 Aug 2.