PMID- 34348977
OWN - NLM
STAT- MEDLINE
DCOM- 20210831
LR  - 20220902
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 207
IP  - 5
DP  - 2021 Sep 1
TI  - Activation of Transcription Factor 4 in Dendritic Cells Controls Th1/Th17 
      Responses and Autoimmune Neuroinflammation.
PG  - 1428-1436
LID - 10.4049/jimmunol.2100010 [doi]
AB  - Dendritic cells (DCs) are professional APCs that play a crucial role in 
      initiating robust immune responses against invading pathogens while inducing 
      regulatory responses to the body's tissues and commensal microorganisms. A 
      breakdown of DC-mediated immunological tolerance leads to chronic inflammation 
      and autoimmune disorders. However, cell-intrinsic molecular regulators that are 
      critical for programming DCs to a regulatory state rather than to an inflammatory 
      state are not known. In this study, we show that the activation of the TCF4 
      transcription factor in DCs is critical for controlling the magnitude of 
      inflammatory responses and limiting neuroinflammation. DC-specific deletion of 
      TCF4 in mice increased Th1/Th17 responses and exacerbated experimental autoimmune 
      encephalomyelitis pathology. Mechanistically, loss of TCF4 in DCs led to 
      heightened activation of p38 MAPK and increased levels of proinflammatory 
      cytokines IL-6, IL-23, IL-1beta, TNF-alpha, and IL-12p40. Consistent with these 
      findings, pharmacological blocking of p38 MAPK activation delayed experimental 
      autoimmune encephalomyelitis onset and diminished CNS pathology in TCF4(DeltaDC) 
      mice. Thus, manipulation of the TCF4 pathway in DCs could provide novel 
      opportunities for regulating chronic inflammation and represents a potential 
      therapeutic approach to control autoimmune neuroinflammation.
CI  - Copyright (c) 2021 by The American Association of Immunologists, Inc.
FAU - Manoharan, Indumathi
AU  - Manoharan I
AD  - Department of Biochemistry and Molecular Biology, Medical College of Georgia, 
      Augusta University, Augusta, GA.
AD  - Georgia Cancer Center, Medical College of Georgia, Augusta University, Augusta, 
      GA.
FAU - Swafford, Daniel
AU  - Swafford D
AD  - Georgia Cancer Center, Medical College of Georgia, Augusta University, Augusta, 
      GA.
FAU - Shanmugam, Arulkumaran
AU  - Shanmugam A
AD  - Georgia Cancer Center, Medical College of Georgia, Augusta University, Augusta, 
      GA.
FAU - Patel, Nikhil
AU  - Patel N
AUID- ORCID: 0000-0001-9335-0082
AD  - Department of Pathology, Medical College of Georgia, Augusta University, Augusta, 
      GA; and.
FAU - Prasad, Puttur D
AU  - Prasad PD
AUID- ORCID: 0000-0002-8455-0186
AD  - Department of Biochemistry and Molecular Biology, Medical College of Georgia, 
      Augusta University, Augusta, GA.
FAU - Thangaraju, Muthusamy
AU  - Thangaraju M
AD  - Department of Biochemistry and Molecular Biology, Medical College of Georgia, 
      Augusta University, Augusta, GA.
FAU - Manicassamy, Santhakumar
AU  - Manicassamy S
AUID- ORCID: 0000-0002-2203-3917
AD  - Department of Biochemistry and Molecular Biology, Medical College of Georgia, 
      Augusta University, Augusta, GA; smanicassamy@augusta.edu.
AD  - Georgia Cancer Center, Medical College of Georgia, Augusta University, Augusta, 
      GA.
AD  - Department of Medicine, Medical College of Georgia, Augusta University, Augusta, 
      GA.
LA  - eng
GR  - R01 DK097271/DK/NIDDK NIH HHS/United States
GR  - R01 DK123360/DK/NIDDK NIH HHS/United States
GR  - R21 AI156103/AI/NIAID NIH HHS/United States
PT  - Comment
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20210804
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Transcription Factor 4)
SB  - IM
CON - J Immunol. 2021 Sep 1;207(5):1223-1224. PMID: 34426516
MH  - Animals
MH  - Dendritic Cells
MH  - *Encephalomyelitis, Autoimmune, Experimental
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - *Th1 Cells
MH  - Th17 Cells
MH  - Transcription Factor 4
PMC - PMC8415100
MID - NIHMS1721021
COIS- Conflict of Interest: Authors disclose no conflict of interest.
EDAT- 2021/08/06 06:00
MHDA- 2021/09/01 06:00
PMCR- 2022/09/01
CRDT- 2021/08/05 05:43
PHST- 2021/01/07 00:00 [received]
PHST- 2021/06/28 00:00 [accepted]
PHST- 2021/08/06 06:00 [pubmed]
PHST- 2021/09/01 06:00 [medline]
PHST- 2021/08/05 05:43 [entrez]
PHST- 2022/09/01 00:00 [pmc-release]
AID - jimmunol.2100010 [pii]
AID - 10.4049/jimmunol.2100010 [doi]
PST - ppublish
SO  - J Immunol. 2021 Sep 1;207(5):1428-1436. doi: 10.4049/jimmunol.2100010. Epub 2021 
      Aug 4.