PMID- 32499518
OWN - NLM
STAT- MEDLINE
DCOM- 20210319
LR  - 20210604
IS  - 2041-4889 (Electronic)
VI  - 11
IP  - 6
DP  - 2020 Jun 4
TI  - TonEBP in dendritic cells mediates pro-inflammatory maturation and Th1/Th17 
      responses.
PG  - 421
LID - 10.1038/s41419-020-2632-8 [doi]
LID - 421
AB  - Dendritic cells (DCs) are potent antigen-presenting cells that link the innate 
      and adaptive immune responses; as such they play pivotal roles in initiation and 
      progression of rheumatoid arthritis (RA). Here, we report that the 
      tonicity-responsive enhancer-binding protein (TonEBP or NFAT5), a Rel family 
      protein involved in the pathogenesis of autoimmune disease and inflammation, is 
      required for maturation and function of DCs. Myeloid cell-specific TonEBP 
      deletion reduces disease severity in a murine model of collagen-induced 
      arthritis; it also inhibits maturation of DCs and differentiation of pathogenic 
      Th1 and Th17 cells in vivo. Upon stimulation by TLR4, TonEBP promotes surface 
      expression of major histocompatibility complex class II and co-stimulatory 
      molecules via p38 mitogen-activated protein kinase. This is followed by 
      DC-mediated differentiation of pro-inflammatory Th1 and Th17 cells. Taken 
      together, these findings provide mechanistic basis for the pathogenic role of 
      TonEBP in RA and possibly other autoimmune diseases.
FAU - Ye, Byeong Jin
AU  - Ye BJ
AD  - School of Life Sciences, Ulsan National Institute of Science and Technology, 
      Ulsan, 44919, Republic of Korea.
FAU - Lee, Hwan Hee
AU  - Lee HH
AD  - School of Life Sciences, Ulsan National Institute of Science and Technology, 
      Ulsan, 44919, Republic of Korea.
FAU - Yoo, Eun Jin
AU  - Yoo EJ
AD  - School of Life Sciences, Ulsan National Institute of Science and Technology, 
      Ulsan, 44919, Republic of Korea.
FAU - Lee, Chae Young
AU  - Lee CY
AD  - School of Life Sciences, Ulsan National Institute of Science and Technology, 
      Ulsan, 44919, Republic of Korea.
FAU - Lee, Jun Ho
AU  - Lee JH
AD  - School of Life Sciences, Ulsan National Institute of Science and Technology, 
      Ulsan, 44919, Republic of Korea.
FAU - Kang, Hyun Je
AU  - Kang HJ
AD  - School of Life Sciences, Ulsan National Institute of Science and Technology, 
      Ulsan, 44919, Republic of Korea.
FAU - Jeong, Gyu Won
AU  - Jeong GW
AD  - School of Life Sciences, Ulsan National Institute of Science and Technology, 
      Ulsan, 44919, Republic of Korea.
FAU - Park, Hyun
AU  - Park H
AD  - School of Life Sciences, Ulsan National Institute of Science and Technology, 
      Ulsan, 44919, Republic of Korea.
FAU - Lee-Kwon, Whaseon
AU  - Lee-Kwon W
AD  - School of Life Sciences, Ulsan National Institute of Science and Technology, 
      Ulsan, 44919, Republic of Korea.
FAU - Choi, Soo Youn
AU  - Choi SY
AUID- ORCID: 0000-0002-3149-5590
AD  - School of Life Sciences, Ulsan National Institute of Science and Technology, 
      Ulsan, 44919, Republic of Korea. sychoi@unist.ac.kr.
FAU - Kwon, Hyug Moo
AU  - Kwon HM
AD  - School of Life Sciences, Ulsan National Institute of Science and Technology, 
      Ulsan, 44919, Republic of Korea. hmkwon@unist.ac.kr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200604
PL  - England
TA  - Cell Death Dis
JT  - Cell death & disease
JID - 101524092
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NFATC Transcription Factors)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Arthritis, Experimental/immunology/pathology
MH  - Cell Differentiation/immunology
MH  - Cell Proliferation
MH  - Dendritic Cells/*metabolism
MH  - Disease Models, Animal
MH  - Inflammation/*immunology
MH  - Lipopolysaccharides
MH  - Lymphocyte Activation/immunology
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Models, Biological
MH  - Myeloid Cells/metabolism
MH  - NFATC Transcription Factors/deficiency/*metabolism
MH  - Severity of Illness Index
MH  - T-Lymphocytes/immunology
MH  - Th1 Cells/*immunology
MH  - Th17 Cells/*immunology
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
PMC - PMC7272407
COIS- The authors declare that they have no conflict of interest.
EDAT- 2020/06/06 06:00
MHDA- 2021/03/20 06:00
PMCR- 2020/06/04
CRDT- 2020/06/06 06:00
PHST- 2019/12/09 00:00 [received]
PHST- 2020/05/21 00:00 [accepted]
PHST- 2020/05/19 00:00 [revised]
PHST- 2020/06/06 06:00 [entrez]
PHST- 2020/06/06 06:00 [pubmed]
PHST- 2021/03/20 06:00 [medline]
PHST- 2020/06/04 00:00 [pmc-release]
AID - 10.1038/s41419-020-2632-8 [pii]
AID - 2632 [pii]
AID - 10.1038/s41419-020-2632-8 [doi]
PST - epublish
SO  - Cell Death Dis. 2020 Jun 4;11(6):421. doi: 10.1038/s41419-020-2632-8.