PMID- 33423291
OWN - NLM
STAT- MEDLINE
DCOM- 20210927
LR  - 20240226
IS  - 1365-2249 (Electronic)
IS  - 0009-9104 (Print)
IS  - 0009-9104 (Linking)
VI  - 204
IP  - 1
DP  - 2021 Apr
TI  - IRF5 regulates airway macrophage metabolic responses.
PG  - 134-143
LID - 10.1111/cei.13573 [doi]
AB  - Interferon regulatory factor 5 (IRF5) is a master regulator of macrophage 
      phenotype and a key transcription factor involved in expression of 
      proinflammatory cytokine responses to microbial and viral infection. Here, we 
      show that IRF5 controls cellular and metabolic responses. By integrating ChIP 
      sequencing (ChIP-Seq) and assay for transposase-accessible chromatin using 
      sequencing (ATAC)-seq data sets, we found that IRF5 directly regulates metabolic 
      genes such as hexokinase-2 (Hk2). The interaction of IRF5 and metabolic genes had 
      a functional consequence, as Irf5(-/-) airway macrophages but not bone 
      marrow-derived macrophages (BMDMs) were characterized by a quiescent metabolic 
      phenotype at baseline and had reduced ability to utilize oxidative 
      phosphorylation after Toll-like receptor (TLR)-3 activation, in comparison to 
      controls, ex vivo. In a murine model of influenza infection, IRF5 deficiency had 
      no effect on viral load in comparison to wild-type controls but controlled 
      metabolic responses to viral infection, as IRF5 deficiency led to reduced 
      expression of Sirt6 and Hk2. Together, our data indicate that IRF5 is a key 
      component of AM metabolic responses following influenza infection and TLR-3 
      activation.
CI  - (c) 2021 The Authors. Clinical & Experimental Immunology published by John Wiley & 
      Sons Ltd on behalf of British Society for Immunology.
FAU - Albers, G J
AU  - Albers GJ
AUID- ORCID: 0000-0002-8249-6956
AD  - Inflammation, Repair and Development Section, National Heart and Lung Institute, 
      Imperial College London, London, UK.
FAU - Iwasaki, J
AU  - Iwasaki J
AUID- ORCID: 0000-0002-5833-7146
AD  - Inflammation, Repair and Development Section, National Heart and Lung Institute, 
      Imperial College London, London, UK.
FAU - McErlean, P
AU  - McErlean P
AD  - Inflammation, Repair and Development Section, National Heart and Lung Institute, 
      Imperial College London, London, UK.
FAU - Ogger, P P
AU  - Ogger PP
AUID- ORCID: 0000-0002-2698-3565
AD  - Inflammation, Repair and Development Section, National Heart and Lung Institute, 
      Imperial College London, London, UK.
FAU - Ghai, P
AU  - Ghai P
AD  - Inflammation, Repair and Development Section, National Heart and Lung Institute, 
      Imperial College London, London, UK.
FAU - Khoyratty, T E
AU  - Khoyratty TE
AD  - The Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK.
FAU - Udalova, I A
AU  - Udalova IA
AUID- ORCID: 0000-0002-6716-2528
AD  - The Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK.
FAU - Lloyd, C M
AU  - Lloyd CM
AUID- ORCID: 0000-0001-8977-6726
AD  - Inflammation, Repair and Development Section, National Heart and Lung Institute, 
      Imperial College London, London, UK.
FAU - Byrne, A J
AU  - Byrne AJ
AUID- ORCID: 0000-0003-2736-8174
AD  - Inflammation, Repair and Development Section, National Heart and Lung Institute, 
      Imperial College London, London, UK.
LA  - eng
GR  - 209422/Z/17/Z/WT_/Wellcome Trust/United Kingdom
GR  - AUK-SNF-2017- 381/Asthma UK/
GR  - 107059/Z/15/Z/Wellcome/
GR  - WT_/Wellcome Trust/United Kingdom
GR  - 100156/Z/12/Z/WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210128
PL  - England
TA  - Clin Exp Immunol
JT  - Clinical and experimental immunology
JID - 0057202
RN  - 0 (Interferon Regulatory Factors)
RN  - 0 (Toll-Like Receptor 3)
RN  - EC 2.4.2.31 (Sirt6 protein, mouse)
RN  - EC 2.7.1.1 (Hexokinase)
RN  - EC 2.7.1.1 (hexokinase 2, mouse)
RN  - EC 3.5.1.- (Sirtuins)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Chromatin Immunoprecipitation Sequencing/methods
MH  - Energy Metabolism/genetics/*immunology
MH  - Female
MH  - Gene Expression Regulation/*immunology
MH  - Hexokinase/genetics/immunology/metabolism
MH  - Humans
MH  - Interferon Regulatory Factors/genetics/*immunology/metabolism
MH  - Macrophages/*immunology/metabolism
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Respiratory System/*cytology
MH  - Sirtuins/genetics/immunology/metabolism
MH  - Toll-Like Receptor 3/genetics/immunology/metabolism
MH  - Mice
PMC - PMC7944363
OTO - NOTNLM
OT  - lung
OT  - macrophage
OT  - metabolism
OT  - transcription factors
OT  - virus
COIS- A. J. B. received, unrelated to the submitted work, consultancy fees from Devpro 
      and Ionis pharmaceuticals and received consultancy fees/industry-academic 
      funding from Ammax pharmaceuticals, via his institution.
EDAT- 2021/01/11 06:00
MHDA- 2021/09/28 06:00
PMCR- 2021/01/28
CRDT- 2021/01/10 20:51
PHST- 2020/10/04 00:00 [received]
PHST- 2020/12/13 00:00 [revised]
PHST- 2020/12/16 00:00 [accepted]
PHST- 2021/01/11 06:00 [pubmed]
PHST- 2021/09/28 06:00 [medline]
PHST- 2021/01/10 20:51 [entrez]
PHST- 2021/01/28 00:00 [pmc-release]
AID - CEI13573 [pii]
AID - 10.1111/cei.13573 [doi]
PST - ppublish
SO  - Clin Exp Immunol. 2021 Apr;204(1):134-143. doi: 10.1111/cei.13573. Epub 2021 Jan 
      28.