PMID- 31522122
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200928
IS  - 2589-0042 (Electronic)
IS  - 2589-0042 (Linking)
VI  - 19
DP  - 2019 Sep 27
TI  - NCoR1: Putting the Brakes on the Dendritic Cell Immune Tolerance.
PG  - 996-1011
LID - S2589-0042(19)30302-5 [pii]
LID - 10.1016/j.isci.2019.08.024 [doi]
AB  - Understanding the mechanisms fine-tuning immunogenic versus tolerogenic balance 
      in dendritic cells (DCs) is of high importance for therapeutic approaches. We 
      found that NCoR1-mediated direct repression of the tolerogenic program in 
      conventional DCs is essential for induction of an optimal immunogenic response. 
      NCoR1 depletion upregulated a wide variety of tolerogenic genes in activated DCs, 
      which consequently resulted in increased frequency of FoxP3(+) regulatory 
      T cells. Mechanistically, NCoR1 masks the PU.1-bound super-enhancers on major 
      tolerogenic genes after DC activation that are subsequently bound by nuclear 
      factor-kappaB. NCoR1 knockdown (KD) reduced RelA nuclear translocation and activity, 
      whereas RelB was unaffected, providing activated DCs a tolerogenic advantage. 
      Moreover, NCoR1(DC-/-) mice depicted enhanced Tregs in draining lymph nodes with 
      increased disease burden upon bacterial and parasitic infections. Besides, 
      adoptive transfer of activated NCoR1 KD DCs in infected animals showed a similar 
      phenotype. Collectively, our results demonstrated NCoR1 as a promising target to 
      control DC-mediated immune tolerance.
CI  - Copyright (c) 2019 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Ahad, Abdul
AU  - Ahad A
AD  - Immuno-genomics & Systems Biology Laboratory, Institute of Life Sciences (ILS), 
      Bhubaneswar, Odisha 751023, India; Manipal Academy of Higher Education, Manipal, 
      Karnataka 576104, India.
FAU - Stevanin, Mathias
AU  - Stevanin M
AD  - Department of Biochemistry CIIL, University of Lausanne (UNIL), Epalinges 
      CH-1066, Switzerland.
FAU - Smita, Shuchi
AU  - Smita S
AD  - Immuno-genomics & Systems Biology Laboratory, Institute of Life Sciences (ILS), 
      Bhubaneswar, Odisha 751023, India; Manipal Academy of Higher Education, Manipal, 
      Karnataka 576104, India.
FAU - Mishra, Gyan Prakash
AU  - Mishra GP
AD  - Immuno-genomics & Systems Biology Laboratory, Institute of Life Sciences (ILS), 
      Bhubaneswar, Odisha 751023, India; Department of Biotechnology, Kalinga Institute 
      of Industrial Technology (KIIT), Bhubaneswar, Odisha 751024, India.
FAU - Gupta, Dheerendra
AU  - Gupta D
AD  - Immuno-genomics & Systems Biology Laboratory, Institute of Life Sciences (ILS), 
      Bhubaneswar, Odisha 751023, India.
FAU - Waszak, Sebastian
AU  - Waszak S
AD  - European Molecular Biology Laboratory (EMBL), Heidelberg 69117, Germany.
FAU - Sarkar, Uday Aditya
AU  - Sarkar UA
AD  - Systems Immunology Laboratory, National Institute of Immunology (NII), Aruna Asaf 
      Ali Marg, New Delhi 110067, India.
FAU - Basak, Soumen
AU  - Basak S
AD  - Systems Immunology Laboratory, National Institute of Immunology (NII), Aruna Asaf 
      Ali Marg, New Delhi 110067, India.
FAU - Gupta, Bhawna
AU  - Gupta B
AD  - Department of Biotechnology, Kalinga Institute of Industrial Technology (KIIT), 
      Bhubaneswar, Odisha 751024, India.
FAU - Acha-Orbea, Hans
AU  - Acha-Orbea H
AD  - Department of Biochemistry CIIL, University of Lausanne (UNIL), Epalinges 
      CH-1066, Switzerland. Electronic address: hans.acha-orbea@unil.ch.
FAU - Raghav, Sunil Kumar
AU  - Raghav SK
AD  - Immuno-genomics & Systems Biology Laboratory, Institute of Life Sciences (ILS), 
      Bhubaneswar, Odisha 751023, India; Manipal Academy of Higher Education, Manipal, 
      Karnataka 576104, India; Department of Biotechnology, Kalinga Institute of 
      Industrial Technology (KIIT), Bhubaneswar, Odisha 751024, India. Electronic 
      address: sunilraghav@ils.res.in.
LA  - eng
PT  - Journal Article
DEP - 20190817
PL  - United States
TA  - iScience
JT  - iScience
JID - 101724038
PMC - PMC6744395
OTO - NOTNLM
OT  - Immune Response
OT  - Immunology
OT  - Molecular Mechanism of Gene Regulation
OT  - Transcriptomics
COIS- The authors declare no competing interests.
EDAT- 2019/09/16 06:00
MHDA- 2019/09/16 06:01
PMCR- 2019/08/17
CRDT- 2019/09/16 06:00
PHST- 2019/02/27 00:00 [received]
PHST- 2019/06/19 00:00 [revised]
PHST- 2019/08/13 00:00 [accepted]
PHST- 2019/09/16 06:00 [pubmed]
PHST- 2019/09/16 06:01 [medline]
PHST- 2019/09/16 06:00 [entrez]
PHST- 2019/08/17 00:00 [pmc-release]
AID - S2589-0042(19)30302-5 [pii]
AID - 10.1016/j.isci.2019.08.024 [doi]
PST - ppublish
SO  - iScience. 2019 Sep 27;19:996-1011. doi: 10.1016/j.isci.2019.08.024. Epub 2019 Aug 
      17.