PMID- 35461286
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220716
IS  - 2045-3701 (Print)
IS  - 2045-3701 (Electronic)
IS  - 2045-3701 (Linking)
VI  - 12
IP  - 1
DP  - 2022 Apr 23
TI  - Aryl hydrocarbon receptor activation ameliorates experimental colitis by 
      modulating the tolerogenic dendritic and regulatory T cell formation.
PG  - 46
LID - 10.1186/s13578-022-00780-z [doi]
LID - 46
AB  - BACKGROUND: Intestinal immune dysfunction is involved in the onset of Crohn's 
      disease (CD). Dendritic cells (DCs), antigen-presenting cells, play a key role in 
      the maintenance of intestinal immune homeostasis. The aryl hydrocarbon receptor 
      (AhR) is a ligand-dependent transcription factor widely expressed in various 
      immune cells, including DCs. Although AhR plays an important role in immune 
      tolerance, its role in the DCs is unclear. The purpose of this study was to 
      investigate whether the activation of AhR can induce tolerogenic DCs (tolDCs) and 
      the differentiation of regulatory T (Treg) cells, as well as ameliorate 
      experimental colitis. RESULTS: AhR activation in the DCs resulted in a lower 
      expression of surface markers such as CD80, CD83, CD86, and pro-inflammatory 
      cytokine production, and higher anti-inflammatory production (IL-1beta, IL-23, and 
      IL-12) compared to the control DCs. The surface dendrites in DCs were 
      significantly reduced following AhR activation by 6-formylindolo [3,2-b]carbazole 
      (FICZ). Such DCs with FICZ-mediated activation of AhR, namely tolDCs, promoted 
      Treg cell differentiation. Adoptive transfer of tolDCs to a TNBS-induced colitis 
      mouse model significantly alleviated the severity of inflammation by improving 
      the colon length and decreasing the disease activity index (DAI) and 
      histopathological score. Moreover, the transferred tolDCs decreased the frequency 
      of Th17 cells and increased the frequency of Treg cells in the spleen and 
      mesenteric lymph nodes (MLNs) in murine colitis models. CONCLUSIONS: Activation 
      of AhR in the DCs could induce tolDCs, and the transplantation of tolDCs may help 
      in relieving intestinal inflammation and maintaining the Th17/Treg 
      differentiation balance. Thus, our data suggest that AhR may be a potential 
      therapeutic target for CD.
CI  - (c) 2022. The Author(s).
FAU - Cui, Xiufang
AU  - Cui X
AD  - Department of Gastroenterology, Nanjing First Hospital, Nanjing Medical 
      University, Nanjing, Jiangsu Province, China.
AD  - Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical 
      University, 300# Guangzhou Road, Nanjing, 210029, Jiangsu, People's Republic of 
      China.
FAU - Ye, Ziping
AU  - Ye Z
AD  - Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical 
      University, 300# Guangzhou Road, Nanjing, 210029, Jiangsu, People's Republic of 
      China.
FAU - Wang, Di
AU  - Wang D
AD  - Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical 
      University, 300# Guangzhou Road, Nanjing, 210029, Jiangsu, People's Republic of 
      China.
FAU - Yang, Yan
AU  - Yang Y
AD  - Department of Gastroenterology, Sir Run Run Hospital, Nanjing Medical University, 
      Nanjing, 211100, Jiangsu, People's Republic of China.
FAU - Jiao, ChunHua
AU  - Jiao C
AD  - Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical 
      University, 300# Guangzhou Road, Nanjing, 210029, Jiangsu, People's Republic of 
      China.
FAU - Ma, Jingjing
AU  - Ma J
AD  - Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical 
      University, 300# Guangzhou Road, Nanjing, 210029, Jiangsu, People's Republic of 
      China.
FAU - Tang, Nana
AU  - Tang N
AD  - Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical 
      University, 300# Guangzhou Road, Nanjing, 210029, Jiangsu, People's Republic of 
      China.
FAU - Zhang, Hongjie
AU  - Zhang H
AUID- ORCID: 0000-0003-4497-0503
AD  - Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical 
      University, 300# Guangzhou Road, Nanjing, 210029, Jiangsu, People's Republic of 
      China. hjzhang06@163.com.
LA  - eng
GR  - 82070568/National Natural Science Foundation of China/
GR  - 81770553/National Natural Science Foundation of China/
GR  - JX10213640/Postgraduate Research & Practice Innovation Program of Jiangsu 
      Province/
PT  - Journal Article
DEP - 20220423
PL  - England
TA  - Cell Biosci
JT  - Cell & bioscience
JID - 101561195
PMC - PMC9034494
OTO - NOTNLM
OT  - Aryl hydrocarbon receptor
OT  - Crohn's disease
OT  - Dendritic cells
OT  - Intestinal immune tolerance
OT  - Treg cells
COIS- The authors declare that they have no conflict of interest.
EDAT- 2022/04/25 06:00
MHDA- 2022/04/25 06:01
PMCR- 2022/04/23
CRDT- 2022/04/24 20:05
PHST- 2020/09/09 00:00 [received]
PHST- 2022/03/30 00:00 [accepted]
PHST- 2022/04/24 20:05 [entrez]
PHST- 2022/04/25 06:00 [pubmed]
PHST- 2022/04/25 06:01 [medline]
PHST- 2022/04/23 00:00 [pmc-release]
AID - 10.1186/s13578-022-00780-z [pii]
AID - 780 [pii]
AID - 10.1186/s13578-022-00780-z [doi]
PST - epublish
SO  - Cell Biosci. 2022 Apr 23;12(1):46. doi: 10.1186/s13578-022-00780-z.