PMID- 34968772
OWN - NLM
STAT- MEDLINE
DCOM- 20220223
LR  - 20220223
IS  - 1090-2163 (Electronic)
IS  - 0008-8749 (Linking)
VI  - 371
DP  - 2022 Jan
TI  - IRF8 and BATF3 interaction enhances the cDC1 specific Pfkfb3 gene expression.
PG  - 104468
LID - S0008-8749(21)00187-8 [pii]
LID - 10.1016/j.cellimm.2021.104468 [doi]
AB  - Dendritic cells (DCs) play central role in innate as well as adaptive immune 
      responses regulated by diverse DC subtypes that vary in terms of surface markers, 
      transcriptional profile and functional responses. Generation of DC diversity from 
      progenitor stage is tightly regulated by complex molecular inter-play between 
      transcription factors. We earlier demonstrated that Batf3 and Id2 expression have 
      a synergistic effect on the Irf8 directed classical cDC1 development. In present 
      study, Bi-molecular fluorescence complementation assay suggested that IRF8 
      interacts with BATF3, and ID2 may aid cDC1 development independently. Genome wide 
      recruitment analysis of IRF8 and BATF3 from different DC subtypes led to 
      identification of the overlapping regions of occupancy by these two transcription 
      factors. Further analysis of overlapping peaks of IRF8 and BATF3 occupancy in 
      promoter region within the cDC1 subtype specific transcriptional pattern 
      identified a metabolically important Pfkfb3 gene. Among various immune cell 
      types; splenic cDC1 subtype displayed enhanced expression of Pfkfb3. Analysis of 
      Irf8(-/-), Irf8(R294C) and Batf3(DCKO) DC confirmed direct regulation of Pfkfb3 
      enhanced expression specifically in cDC1 subtype. Further we show that inhibition 
      of PFKFB3 enzymatic activity by a chemical agent PFK15 led to reduction in cDC1 
      subtype in both in vitro FLDC cultures as well as in vivo mouse spleens. 
      Together, our study identified the direct regulation of cDC1 specific enhanced 
      expression of Pfkfb3 in glycolysis and cDC1 biology.
CI  - Copyright (c) 2021 Elsevier Inc. All rights reserved.
FAU - Chauhan, Kuldeep Singh
AU  - Chauhan KS
AD  - Laboratory of Innate Immunity, National Institute of Immunology, New Delhi, 
      India; Department of Molecular Microbiology, Washington University School of 
      Medicine, St. Louis, MO, USA(1).
FAU - Das, Annesa
AU  - Das A
AD  - Laboratory of Innate Immunity, National Institute of Immunology, New Delhi, 
      India.
FAU - Jaiswal, Hemant
AU  - Jaiswal H
AD  - Laboratory of Innate Immunity, National Institute of Immunology, New Delhi, 
      India; Laboratory of Molecular Immunology, National Institute of Allergy and, 
      Infectious Diseases, National Institutes of Health, Bethesda, MD, USA(2).
FAU - Saha, Irene
AU  - Saha I
AD  - Laboratory of Innate Immunity, National Institute of Immunology, New Delhi, 
      India; Division of Immunobiology, Cincinnati Children's Hospital Medical Center, 
      Cincinnati, OH, USA(3).
FAU - Kaushik, Monika
AU  - Kaushik M
AD  - Laboratory of Innate Immunity, National Institute of Immunology, New Delhi, 
      India; School of Biotechnology, Jawaharlal Nehru University, New Delhi, India(4).
FAU - Patel, Virendra Kumar
AU  - Patel VK
AD  - Cell Biology Laboratory, National Institute of Immunology, New Delhi, India.
FAU - Tailor, Prafullakumar
AU  - Tailor P
AD  - Laboratory of Innate Immunity, National Institute of Immunology, New Delhi, 
      India; Special Centre for Systems Medicine (SCSM), Jawaharlal Nehru University, 
      New Delhi, India. Electronic address: tailorp@nii.ac.in.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20211210
PL  - Netherlands
TA  - Cell Immunol
JT  - Cellular immunology
JID - 1246405
RN  - 0 (Batf3 protein, rat)
RN  - 0 (Interferon Regulatory Factors)
RN  - 0 (PFK15)
RN  - 0 (Pyridines)
RN  - 0 (Quinolines)
RN  - 0 (Repressor Proteins)
RN  - 0 (interferon regulatory factor-8)
RN  - EC 2.7.1.105 (Pfkfb3 protein, rat)
RN  - EC 2.7.1.105 (Phosphofructokinase-2)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Dendritic Cells/*immunology
MH  - Female
MH  - Gene Expression Regulation/genetics
MH  - Glycolysis/genetics
MH  - HEK293 Cells
MH  - Humans
MH  - Interferon Regulatory Factors/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Phosphofructokinase-2/antagonists & inhibitors/*biosynthesis/genetics
MH  - Promoter Regions, Genetic/genetics
MH  - Pyridines/pharmacology
MH  - Quinolines/pharmacology
MH  - Repressor Proteins/*metabolism
OTO - NOTNLM
OT  - Basic leucine zipper transcription factor ATF-like-3 (BATF3)
OT  - CD8alpha(+) DCs
OT  - Dendritic cell development
OT  - Innate Immunity
OT  - Interferon Regulatory Factor-8 (IRF8)
OT  - Transcriptional regulation
EDAT- 2021/12/31 06:00
MHDA- 2022/02/24 06:00
CRDT- 2021/12/30 20:16
PHST- 2021/06/05 00:00 [received]
PHST- 2021/11/27 00:00 [revised]
PHST- 2021/11/28 00:00 [accepted]
PHST- 2021/12/31 06:00 [pubmed]
PHST- 2022/02/24 06:00 [medline]
PHST- 2021/12/30 20:16 [entrez]
AID - S0008-8749(21)00187-8 [pii]
AID - 10.1016/j.cellimm.2021.104468 [doi]
PST - ppublish
SO  - Cell Immunol. 2022 Jan;371:104468. doi: 10.1016/j.cellimm.2021.104468. Epub 2021 
      Dec 10.