PMID- 35864954
OWN - NLM
STAT- MEDLINE
DCOM- 20220725
LR  - 20220812
IS  - 1449-2288 (Electronic)
IS  - 1449-2288 (Linking)
VI  - 18
IP  - 11
DP  - 2022
TI  - Lithocholic acid inhibits dendritic cell activation by reducing intracellular 
      glutathione via TGR5 signaling.
PG  - 4545-4559
LID - 10.7150/ijbs.71287 [doi]
AB  - Dendritic cells (DCs) are the major antigen-presenting cells and play an 
      important role in autoimmune uveitis. Emerging evidence suggests that bile acids 
      (BAs) regulate DCs maturation. However, the underlying mechanisms by which BAs 
      regulate the function of DCs still need to be clarified. Here, we demonstrate 
      that lithocholic acid (LCA) inhibits the production of pro-inflammatory cytokines 
      and the expression of surface molecules in bone marrow-derived dendritic cells 
      (BMDCs). LCA attenuates the severity of EAU by modulating the maturation of 
      splenic CD11C(+)MHCII(high) DCs. Notably, Takeda G-protein coupled receptor 5 
      (TGR5) deficiency partially reverses the inhibitory effect of LCA on DCs in vitro 
      and in vivo. TGR5 activation also downregulates the NF-kappaB and MAPK pathways by 
      inhibiting glutathione production and inducing oxidative stress in DCs, which 
      leads to apoptosis and autophagy in DCs. In addition, LCA or INT-777 treatment 
      increases the TGR5 expression in monocyte-derived dendritic cells (MD-DCs) of 
      patients with active BD, whereas both LCA and TGR5 agonists inhibit the 
      activation of MD-DCs. These results suggest that LCA and TGR5 agonists might be 
      potential therapeutic drugs for the treatment of autoimmune uveitis.
CI  - (c) The author(s).
FAU - Hu, Jianping
AU  - Hu J
AD  - The First Affiliated Hospital of Chongqing Medical University, Chongqing Key 
      Laboratory of Ophthalmology, Chongqing Eye Institute, and Chongqing Branch of 
      National Clinical Research Center for Ocular Diseases, Chongqing, P. R. China.
FAU - Zhang, Yiting
AU  - Zhang Y
AD  - The First Affiliated Hospital of Chongqing Medical University, Chongqing Key 
      Laboratory of Ophthalmology, Chongqing Eye Institute, and Chongqing Branch of 
      National Clinical Research Center for Ocular Diseases, Chongqing, P. R. China.
FAU - Yi, Shenglan
AU  - Yi S
AD  - The First Affiliated Hospital of Chongqing Medical University, Chongqing Key 
      Laboratory of Ophthalmology, Chongqing Eye Institute, and Chongqing Branch of 
      National Clinical Research Center for Ocular Diseases, Chongqing, P. R. China.
FAU - Wang, Chaokui
AU  - Wang C
AD  - The First Affiliated Hospital of Chongqing Medical University, Chongqing Key 
      Laboratory of Ophthalmology, Chongqing Eye Institute, and Chongqing Branch of 
      National Clinical Research Center for Ocular Diseases, Chongqing, P. R. China.
FAU - Huang, Xinyue
AU  - Huang X
AD  - The First Affiliated Hospital of Chongqing Medical University, Chongqing Key 
      Laboratory of Ophthalmology, Chongqing Eye Institute, and Chongqing Branch of 
      National Clinical Research Center for Ocular Diseases, Chongqing, P. R. China.
FAU - Pan, Su
AU  - Pan S
AD  - The First Affiliated Hospital of Chongqing Medical University, Chongqing Key 
      Laboratory of Ophthalmology, Chongqing Eye Institute, and Chongqing Branch of 
      National Clinical Research Center for Ocular Diseases, Chongqing, P. R. China.
FAU - Yang, Jinglu
AU  - Yang J
AD  - The First Affiliated Hospital of Chongqing Medical University, Chongqing Key 
      Laboratory of Ophthalmology, Chongqing Eye Institute, and Chongqing Branch of 
      National Clinical Research Center for Ocular Diseases, Chongqing, P. R. China.
FAU - Yuan, Gangxiang
AU  - Yuan G
AD  - The First Affiliated Hospital of Chongqing Medical University, Chongqing Key 
      Laboratory of Ophthalmology, Chongqing Eye Institute, and Chongqing Branch of 
      National Clinical Research Center for Ocular Diseases, Chongqing, P. R. China.
FAU - Tan, Sisi
AU  - Tan S
AD  - The First Affiliated Hospital of Chongqing Medical University, Chongqing Key 
      Laboratory of Ophthalmology, Chongqing Eye Institute, and Chongqing Branch of 
      National Clinical Research Center for Ocular Diseases, Chongqing, P. R. China.
FAU - Li, Hong
AU  - Li H
AD  - The First Affiliated Hospital of Chongqing Medical University, Chongqing Key 
      Laboratory of Ophthalmology, Chongqing Eye Institute, and Chongqing Branch of 
      National Clinical Research Center for Ocular Diseases, Chongqing, P. R. China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220711
PL  - Australia
TA  - Int J Biol Sci
JT  - International journal of biological sciences
JID - 101235568
RN  - 0 (Bile Acids and Salts)
RN  - 0 (GPBAR1 protein, human)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - 5QU0I8393U (Lithocholic Acid)
RN  - GAN16C9B8O (Glutathione)
SB  - IM
MH  - Bile Acids and Salts/metabolism
MH  - *Dendritic Cells/metabolism
MH  - *Glutathione/metabolism
MH  - Humans
MH  - *Lithocholic Acid/pharmacology
MH  - *Receptors, G-Protein-Coupled/genetics
MH  - Signal Transduction
PMC - PMC9295063
OTO - NOTNLM
OT  - Autoimmune disease
OT  - Bile acids
OT  - Dendritic cells
OT  - TGR5
OT  - Uveitis
COIS- Competing Interests: The authors have declared that no competing interest exists.
EDAT- 2022/07/23 06:00
MHDA- 2022/07/26 06:00
PMCR- 2022/01/01
CRDT- 2022/07/22 02:17
PHST- 2022/01/21 00:00 [received]
PHST- 2022/06/26 00:00 [accepted]
PHST- 2022/07/22 02:17 [entrez]
PHST- 2022/07/23 06:00 [pubmed]
PHST- 2022/07/26 06:00 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - ijbsv18p4545 [pii]
AID - 10.7150/ijbs.71287 [doi]
PST - epublish
SO  - Int J Biol Sci. 2022 Jul 11;18(11):4545-4559. doi: 10.7150/ijbs.71287. 
      eCollection 2022.