Immunity As Cornerstone Of Non-Alcoholic Fatty Liver Disease: The Contribution Of Oxidative Stress in The Disease Progression Part2
Mar 02, 2023
5. Conclusions
The complexity of NAFLD pathogenesis does not permit individualized mechanisms to become incontrovertibly responsible for disease development and progression. Consequently, specific and efficient treatments are unavailable yet, making NAFLD a healthcare burden worldwide. However, a determinant that contributes to the knowledge is derived from studies on redox biology and hepatic immunity. It is well known that redox imbalance is involved in chronic liver diseases and all NAFLD stages, highlighting redox alterations as the triggering force of inflammatory response. However, it is still not clear why this happens only to a part of patients. The potential involvement of pre-existing immunity factors should be explored to explain whether redox imbalance affects a susceptible immune system.
Moreover, through studies on redox biology in the immune cells, very recent reports are shedding light on the importance of immune cell metabolism, developing new concepts like trained immunity and indicating new potential therapeutic targets. Therefore, a deeper understanding of the molecular mechanism underlying the crosstalk between redox biology and immunity is eagerly needed to provide a significant contribution to novel therapeutic approaches.
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Author Contributions:
Conceptualization, M.D. and A.F.; Resources, C.L., and G.S.; Writing— Original Draft Preparation, M.D., M.S., M.R.; Visualization, C.L., and A.F.; Supervision, R.V. and A.D.R.; Project Administration, A.F. and M.D. All authors have read and agreed to the published version of the manuscript.
Funding:
This research received no external funding.
Institutional Review Board Statement:
Not applicable.
Informed Consent Statement:
Not applicable.
Data Availability Statement:
Not applicable.
Acknowledgments:
The representation of cellular structures, molecular pathways, and other elements in the figures was created using the graphic support and the available icons offered by the BioRender software.
Conflicts of Interest:
The authors declare no conflict of interest.
Abbreviations
AMPK Adenosine monophosphate-activated protein kinase
AP-1 Activator protein-1
APCs Antigen Presenting Cells
ASK 1 Apoptosis signal-regulating kinase 1
CAFs Cancer-associated fibroblasts
CCL-2 Chemokine (C-C motif) ligand 2
CHOP C/EBP Homologous Protein
COX Cytochrome c oxidase
COX-2 Cyclooxygenase 2
CTLA CD14+ cytotoxic T-lymphocyte-associated protein
CXCL12 Chemokine C-X-C motif ligand 12
CYP Cytochrome P450
DAMPs Damage-associated molecular patterns
DC Dendritic cell
EGF Epidermal growth factor
eIF2a RNA-dependent protein kinase-like ER eukaryotic initiation factor-2 α kinase\
ER Endoplasmic Reticulum
ETC Electron transport chain
FAO Fatty acid oxidation
FFAs Free fatty acids
FGF Fibroblast growth factor
FoxP3 Forkhead box P3
HCC Hepatocellular Carcinoma
HFD High-fat diet
HGF Hepatocyte growth factor
HIF-1α Hypoxia-inducible factor 1-alpha
HLA Human leukocyte antigen
HMGB1 high mobility group box 1 protein
HNE Dydroxinonenal
HO-1 Heme oxygenase-1
HSCs Hepatic stellate cells
ICI Immune checkpoint inhibitors
IFN-γ Interferon γ
IKK Inhibitor of nuclear factor kappa-B kinase
IR Insulin Resistance
IRG1 Immune responsive gene 1
JMJ Jumonji domain-containing
JNK c-Jun-N-terminal kinase
KCs Kupffer cells
KEAP1 Kelch-like ECH-associated protein 1
LPSL lipopolysaccharides
MAA Malondialdehyde-acetaldehyde
MAFLD Metabolic (dysfunction) associated fatty liver disease
MAP3K Mitogen-activated protein kinase kinase kinase
MAPK Mitogen-activated protein kinase.
MCSF Macrophage colony-stimulating factor
MDA Malondialdehyde
MDSCs Myeloid-derived suppressor cells
MMP Matrix metalloproteases
MPT Mitochondrial permeability transition
MS Metabolic Syndrome
mTOR Mammalian target of rapamycin
NAFLD Non-alcoholic fatty liver disease
NASH Non-alcoholic steatohepatitis
NF-κB Nuclear factor kappa-light-chain-enhancer of activated B cells
NK Natural Killer
NLRP NLR family pyrin domain containing
NLRS Nucleotide-binding oligomerization domain-like receptors
NOX NADPH oxidase
Nrf2 Nuclear factor erythroid 2–related factor 2
OLRs Oligoadenylate synthase (OAS)-like receptors
OSEs Oxidation-specific epitopes
OXPHOS Oxidative phosphorylation
PAMPs Pathogen Associated Molecular Patterns
PDGF Platelet-Derived Growth Factor
PPARs Peroxisome proliferator-activated receptor
PD1 Programmed cell Death 1
PRRs Pattern recognition receptors
PUFAs Polyunsaturated fatty acids
RAGEs Receptors for advanced glycation end products
ROS Reactive oxygen species
SDH Succinate dehydrogenase
SNPs Single Nucleotide Polymorphisms
SOD Superoxide dismutase
SPARC Secreted protein acidic rich in cysteine
TAK 1 TGF-β-activated kinase 1
TAMs Tumour-associated macrophages
TET Ten eleven translocation
TGF-β Transforming Growth Factor-β
TI Trained Immunity
TLRs Toll-like receptors
TNF-α Tumor Necrosis Factor-α
TRAIL Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL)
Tregs Regulatory T cells
VEGF Vascular endothelial growth factor
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