PMID- 33527393
OWN - NLM
STAT- MEDLINE
DCOM- 20210927
LR  - 20210927
IS  - 1521-4141 (Electronic)
IS  - 0014-2980 (Linking)
VI  - 51
IP  - 5
DP  - 2021 May
TI  - Zbtb10 transcription factor is crucial for murine cDC1 activation and cytokine 
      secretion.
PG  - 1126-1142
LID - 10.1002/eji.202048933 [doi]
AB  - Dendritic cell (DC) activation and cytokine production is tightly regulated. In 
      this study, we found that Zbtb10 expression is activation dependent and it is 
      essential for the immunogenic function of cDC1. Zbtb10 knockdown (KD) 
      significantly reduced the expression of co-stimulatory genes CD80 and CD86 along 
      with cytokines including IL-12, IL-6, and IL-10, in activated cDC1 Mutu-DC line. 
      Consequently, the clonal expansion of CD44(+) effector T cells in co-cultured 
      CD4(+) T cells was drastically reduced owing to significantly reduced IL-2. At 
      the same time, these CD44(+) effector T cells were unable to differentiate toward 
      Tbet(+) IFNgamma(+) Th1 subtype. Instead, an increased frequency of Th2 cells 
      expressing GATA3(+) and IL-13(+) was observed. Interestingly, in Zbtb10 KD 
      condition the co-cultured T cells depicted increased expression of PD1 and LAG3, 
      the T-cell anergic markers. Moreover, the global transcriptome analysis 
      identified that Zbtb10 is pertinent for DC activation and its depletion in cDC1 
      completely shuts down their immune responses. Mechanistic analysis revealed that 
      Zbtb10 KD enhanced the expression of NKRF (NF-kappaB repressing factor) leading to 
      drastic suppression of NF-kappaB related genes. Zbtb10 KD abrogated p65 and RelB 
      nuclear translocation, thereby controlling the activation and maturation of cDC1 
      and the ensuing adaptive T cell responses.
CI  - (c) 2021 Wiley-VCH GmbH.
FAU - Smita, Shuchi
AU  - Smita S
AD  - Immuno-genomics & Systems Biology group, Institute of Life Sciences, Bhubaneswar, 
      India.
AD  - Department of Biotechnology, Manipal Academy of Higher Education, Manipal, India.
FAU - Ghosh, Arup
AU  - Ghosh A
AD  - Immuno-genomics & Systems Biology group, Institute of Life Sciences, Bhubaneswar, 
      India.
AD  - Department of Biotechnology, Kalinga Institute of Industrial Technology (KIIT), 
      Bhubaneswar, India.
FAU - Biswas, Viplov Kumar
AU  - Biswas VK
AD  - Immuno-genomics & Systems Biology group, Institute of Life Sciences, Bhubaneswar, 
      India.
AD  - Department of Biotechnology, Kalinga Institute of Industrial Technology (KIIT), 
      Bhubaneswar, India.
FAU - Ahad, Abdul
AU  - Ahad A
AD  - Immuno-genomics & Systems Biology group, Institute of Life Sciences, Bhubaneswar, 
      India.
AD  - Department of Biotechnology, Manipal Academy of Higher Education, Manipal, India.
FAU - Podder, Sreeparna
AU  - Podder S
AD  - Immuno-genomics & Systems Biology group, Institute of Life Sciences, Bhubaneswar, 
      India.
AD  - Department of Biotechnology, Kalinga Institute of Industrial Technology (KIIT), 
      Bhubaneswar, India.
FAU - Jha, Atimukta
AU  - Jha A
AD  - Immuno-genomics & Systems Biology group, Institute of Life Sciences, Bhubaneswar, 
      India.
AD  - Department of Biotechnology, Manipal Academy of Higher Education, Manipal, India.
FAU - Sen, Kaushik
AU  - Sen K
AD  - Immuno-genomics & Systems Biology group, Institute of Life Sciences, Bhubaneswar, 
      India.
AD  - Regional Centre for Biotechnology, Faridabad, Haryana, India.
FAU - Acha-Orbea, Hans
AU  - Acha-Orbea H
AD  - Department of Biochemistry CIIL, University of Lausanne (UNIL), Epalinges, 
      Switzerland.
FAU - Raghav, Sunil K
AU  - Raghav SK
AUID- ORCID: 0000-0001-9913-4241
AD  - Immuno-genomics & Systems Biology group, Institute of Life Sciences, Bhubaneswar, 
      India.
AD  - Department of Biotechnology, Manipal Academy of Higher Education, Manipal, India.
AD  - Department of Biotechnology, Kalinga Institute of Industrial Technology (KIIT), 
      Bhubaneswar, India.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210301
PL  - Germany
TA  - Eur J Immunol
JT  - European journal of immunology
JID - 1273201
RN  - 0 (Biomarkers)
RN  - 0 (Cytokines)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Animals
MH  - Biomarkers
MH  - Cell Differentiation/genetics/immunology
MH  - Cell Line
MH  - Cytokines/*biosynthesis
MH  - Dendritic Cells/*immunology/*metabolism
MH  - Gene Expression Profiling
MH  - Gene Expression Regulation
MH  - Lymphocyte Activation/immunology
MH  - Mice
MH  - T-Lymphocyte Subsets/immunology/metabolism
MH  - Transcription Factors/*metabolism
OTO - NOTNLM
OT  - NFkB
OT  - Th1 cells
OT  - Th2 cells
OT  - Zbtb10
OT  - cDC1
EDAT- 2021/02/03 06:00
MHDA- 2021/09/28 06:00
CRDT- 2021/02/02 06:15
PHST- 2020/11/14 00:00 [revised]
PHST- 2020/08/20 00:00 [received]
PHST- 2021/01/28 00:00 [accepted]
PHST- 2021/02/03 06:00 [pubmed]
PHST- 2021/09/28 06:00 [medline]
PHST- 2021/02/02 06:15 [entrez]
AID - 10.1002/eji.202048933 [doi]
PST - ppublish
SO  - Eur J Immunol. 2021 May;51(5):1126-1142. doi: 10.1002/eji.202048933. Epub 2021 
      Mar 1.