PMID- 27891589
OWN - NLM
STAT- MEDLINE
DCOM- 20170508
LR  - 20181113
IS  - 1365-2249 (Electronic)
IS  - 0009-9104 (Print)
IS  - 0009-9104 (Linking)
VI  - 188
IP  - 1
DP  - 2017 Apr
TI  - Critical roles of conventional dendritic cells in promoting T cell-dependent 
      hepatitis through regulating natural killer T cells.
PG  - 127-137
LID - 10.1111/cei.12907 [doi]
AB  - Dendritic cells (DCs) play critical roles in initiating and regulating innate 
      immunity as well as adaptive immune responses. However, the role of conventional 
      dendritic cells (cDCs) in concanavalin A (ConA)-induced fulminant hepatitis is 
      unknown. In this study, we demonstrated that depletion of cDCs using either 
      CD11c-diphtheria toxin receptor transgenic mice (DTR Tg) mice or anti-CD11c 
      antibody reduced the severity of liver injury significantly, indicating a 
      detrimental role of cDCs in ConA-induced hepatitis. We elucidated further the 
      pathological role of cDCs as being the critical source of interleukin (IL)-12, 
      which induced the secretion of interferon (IFN)-gamma by natural killer (NK) T cells. 
      Reconstitution of cDCs-depleted mice with IL-12 restored ConA-induced hepatitis 
      significantly. Furthermore, we determined that NK T cells were the target of 
      DC-derived IL-12, and NK T cells contributed to liver inflammation and injury 
      through production of IFN-gamma. In summary, our study demonstrated a novel function 
      of cDCs in mediating ConA-induced hepatitis through regulating IFN-gamma secretion of 
      NK T cells in an IL-12-dependent fashion. Targeting cDCs might provide 
      potentially therapeutic applications in treating autoimmune related liver 
      diseases.
CI  - (c) 2016 British Society for Immunology.
FAU - Wang, J
AU  - Wang J
AD  - State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, 
      Nankai University, Tianjin, China.
FAU - Cao, X
AU  - Cao X
AD  - State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, 
      Nankai University, Tianjin, China.
FAU - Zhao, J
AU  - Zhao J
AD  - State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, 
      Nankai University, Tianjin, China.
FAU - Zhao, H
AU  - Zhao H
AD  - State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, 
      Nankai University, Tianjin, China.
FAU - Wei, J
AU  - Wei J
AD  - The First Affiliate Hospital, Biomedical Translational Research Institute, 
      Guangdong Province Key Laboratory of Molecular Immunology and Antibody 
      Engineering, Jinan University, Guangzhou, China.
FAU - Li, Q
AU  - Li Q
AD  - State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, 
      Nankai University, Tianjin, China.
FAU - Qi, X
AU  - Qi X
AD  - State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, 
      Nankai University, Tianjin, China.
FAU - Yang, Z
AU  - Yang Z
AD  - State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, 
      Nankai University, Tianjin, China.
FAU - Wang, L
AU  - Wang L
AD  - State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, 
      Nankai University, Tianjin, China.
FAU - Zhang, H
AU  - Zhang H
AD  - State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, 
      Nankai University, Tianjin, China.
FAU - Bai, L
AU  - Bai L
AD  - Collaborative Innovation Center for Biotherapy, Sichuan University, Chengdu, 
      Sichuan, China.
FAU - Wu, Z
AU  - Wu Z
AD  - State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, 
      Nankai University, Tianjin, China.
FAU - Zhao, L
AU  - Zhao L
AD  - State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, 
      Nankai University, Tianjin, China.
FAU - Hong, Z
AU  - Hong Z
AD  - State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, 
      Nankai University, Tianjin, China.
FAU - Yin, Z
AU  - Yin Z
AD  - State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, 
      Nankai University, Tianjin, China.
AD  - Department of Immunology, St Jude Children's Research Hospital, Memphis, TN, USA.
AD  - University of Science and Technology of China, Hefei City, Anhui, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170105
PL  - England
TA  - Clin Exp Immunol
JT  - Clinical and experimental immunology
JID - 0057202
RN  - 0 (Biomarkers)
RN  - 0 (Cytokines)
RN  - 0 (Inflammation Mediators)
SB  - IM
EIN - Clin Exp Immunol. 2018 Dec;194(3):414. PMID: 30417323
MH  - Adoptive Transfer
MH  - Animals
MH  - Biomarkers
MH  - *Cell Communication/immunology
MH  - Cytokines/metabolism
MH  - Dendritic Cells/*immunology/metabolism
MH  - Disease Models, Animal
MH  - Hepatitis/*immunology/metabolism/mortality/pathology
MH  - *Immunomodulation
MH  - Immunophenotyping
MH  - Inflammation Mediators/metabolism
MH  - Liver Failure, Acute/etiology/metabolism/mortality/pathology
MH  - Liver Function Tests
MH  - Mice
MH  - Mice, Transgenic
MH  - Natural Killer T-Cells/*immunology/metabolism
MH  - Phenotype
MH  - T-Lymphocyte Subsets/*immunology/metabolism
PMC - PMC5343358
OTO - NOTNLM
OT  - IFN-gamma
OT  - IL-12
OT  - cDCs
OT  - hepatitis
EDAT- 2016/11/29 06:00
MHDA- 2017/05/10 06:00
PMCR- 2018/04/01
CRDT- 2016/11/29 06:00
PHST- 2016/09/12 00:00 [received]
PHST- 2016/11/12 00:00 [revised]
PHST- 2016/11/21 00:00 [accepted]
PHST- 2016/11/29 06:00 [pubmed]
PHST- 2017/05/10 06:00 [medline]
PHST- 2016/11/29 06:00 [entrez]
PHST- 2018/04/01 00:00 [pmc-release]
AID - CEI12907 [pii]
AID - 10.1111/cei.12907 [doi]
PST - ppublish
SO  - Clin Exp Immunol. 2017 Apr;188(1):127-137. doi: 10.1111/cei.12907. Epub 2017 Jan 
      5.