Autophagy: A Friend or Foe in Allergic Asthma?
Abstract
:1. Mechanisms of Autophagy
2. Autophagy Regulation
3. Transcriptional Control of Autophagy
4. Allergic Asthma Immunopathogenesis
5. Role of Autophagy in Allergic Airway Inflammation In Vivo
6. Activation of Autophagy in Human Asthma
7. Concluding Remarks and Future Perspectives
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
ATG | autophagy-related genes |
LC3 | ATG8/microtubule-associated protein 1 light chain 3 |
TFEB | transcription factor EB |
ROS | reactive oxygen species |
mTORC | mammalian target of rapamycin complex |
AMPK | AMP-activated protein kinase |
SIRTs | sirtuins |
FOXO | forkhead box protein O |
PI3K | phosphatidylinositol 3-kinase |
AKT | protein kinase B |
LPS | lipopolysaccharide |
PBMCs | peripheral blood mononuclear cells |
DCs | dendritic cells |
BCL2 | B-cell CLL/lymphoma 2 |
AHR | Hyperresponsiveness |
BAL | bronchoalveolar lavage fluid |
CS | corticosteroids |
FeNO | nitric oxide |
ASM | airway smooth muscle |
PGA | paucigranulocytic asthma |
ILC2s | type 2 innate lymphoid cells |
TSLP | thymic stromal lymphopoietin |
OVA | ovalbumin |
AAI | allergic airway inflammation |
3-MA | 3-Methyladenine |
HDM | house dust mite |
AMs | alveolar macrophages |
ECRS | eosinophilic chronic rhinosinusitis |
CQ | chloroquine |
HRV1B | Human Rhinovirus 1B |
MHC | major histocompatibility complex |
RSV | respiratory syncytial virus |
BECs | bronchial epithelial cells |
HAECs | airway epithelial cells |
PBNs | peripheral blood neutrophils |
HBF | Human bronchial fibroblasts |
ECM | extracellular matrix |
PE | phosphatidylethanolamine |
p62 | Sequestosome 1 |
LIR | LC3-interacting region |
TSC2 | tuberous sclerosis complex subunit 2 |
CaMKII | Calmodulin-dependent protein kinase II |
FFAs | Free fatty acids |
MiT/TFE | microphthalmia/transcription factor E |
MITF | melanogenesis associated transcription factor |
TFEC | Transcription Factor EC |
TFE3 | Transcription Factor Binding To IGHM Enhancer 3 |
CLEAR | coordinated lysosomal expression and regulation |
GTP | guanosine triphosphate |
RagA | heterodimeric RagGTPases |
YWHA/14-3-3 | 14-3-3 phospho-serine/phospho-treonine binding protein |
ACSS2 | acetyl-CoA synthetase short-chain family member 2 |
NFAT | nuclear factors of activated T cells |
PRKCA | Protein Kinase C Alpha |
GSK3β | Glycogen Synthase Kinase 3 Beta |
DRAM | Damaged-regulated- modulator |
BNIP3 | BCL2 Interacting Protein 3 |
EZH2 | Enhancer of Zeste Homolog 2 |
BRD4 | Bromodomain-containing protein 4 |
CARM1 | co-activator associated histone arginine methyltransferase 1 |
hMOF | Males absent On the First |
FOXK | Forkhead box K |
HDAC | Histone deacetylase |
SA | severe asthma |
NFκB | nuclear factor kappaB |
S1PR2 | Sphingosine-1-phosphate receptor 2 |
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Autophagy Activation | |
---|---|
Treatment | Allergic Airway Disease Outcome |
Mtor−/− bronchial epithelial cells in HDM and/or OVA challenged mice | Increased recruitment of inflammatory cells and eosinophils in the BAL Enhanced mucus accumulation Exacerbated AHR Heightened IL-25 levels |
ILC2-specific TfebTG mice in IL-33-induced AAI | Enhanced ILC2s cell infiltration in the lungs Increased survival and proliferation of ILC2s Enhanced Th2 cytokine release |
Simvastatin administration in OVA-challenged mice | Reduced airway inflammation and remodeling through autophagy activation Attenuated AHR Decreased IL-4, IL-5, IL-13, and IFN-γ levels in the BAL |
Rapamycin administration in acute AAI induced by intravenous transfer of in vitro generated OVA-specific Th17 cells | Reduced pulmonary inflammation Increased recruitment of plasmacytoid dendritic cells Reduction of neutrophilic infiltration in the BAL Reduced CXCL-1 levels in the BAL |
Autophagy Deficiency | |
---|---|
Treatment | Allergic Airway Disease Outcome |
CD11c-specific Atg5−/− mice (HDM mouse model) | Increased IL-1β and IL-23 release Increased AHR Severe neutrophilic and Th17 cell-mediated airway inflammation Glucocorticoid resistance |
Myeloid specific Atg7−/− mice (LPS or bleomycin) | Increased IL-1β, IL-18, and IL-17 levels in the lungs and serum Increased mortality |
Atg7−/− airway epithelial-specific mice | Swelling of bronchial epithelial cells Increased AHR Enhanced airway wall thickening Increased p62 accumulation |
Atg16l1−/− mice (intranasal IL-33 administration) | Attenuated mucus secretion |
3-MA or Atg5−/− mice (OVA-induced severe eosinophilic AAI) | Attenuated AHR Decreased inflammatory cell recruitment in the BAL and lung Reduced IL-5 levels in the BAL |
Lc3-b−/− mice (HDM and/or OVA AAI) | Reduced airway inflammation and mucus production Increased AHR |
Atg5−/− ILC2s specific mice (IL-33-AAI) | Decreased Th2 cytokine release Impaired fatty acid oxidation Attenuated pulmonary inflammation and AHR |
Atg5−/− B cell-specific mice (OVA-induced AAI) | Reduced levels of IL-4, IL-13, and inflammatory cell numbers in the BAL Decreased OVA-specific IgE production Reduced mucus production |
3-MA administration (mouse model of cockroach allergen-induced AAI) | Decreased lung inflammation and mucus production Attenuated AHR Reduced ROS release Decreased Th2 cell-associated cytokines |
3-MA administration (OVA-induced AAI) | Attenuated pulmonary inflammation Reduced eosinophil numbers, eosinophil peroxidase activity, and extracellular DNA concentrations in the BAL Reduced ROS levels Decreased goblet cell hyperplasia |
CQ administration (HDM-induced acute and chronic AAI) | Decreased inflammatory cell infiltration Reduced TGF-β production in the BAL Attenuated AHR Decreased collagen deposition and mucus production Reduced airway remodeling |
Astraglin administration (OVA-induced AAI) | Decreased the subepithelial deposition of collagen fibers through autophagy inhibition |
Luteolin administration (OVA-induced AAI) | Decreased inflammatory cell infiltration Reduced IL-4, IL-5, IL-13 levels in the BAL Decreased collagen deposition and mucus production |
EX-527 administration (OVA-induced AAI) | Decreased airway inflammation Reduced IL-4, IL-13, and IFN-γ levels in the BAL |
JTE-013 administration (OVA-induced chronic AAI) | Decreased inflammatory cell recruitment Reduced IL-1, IL-4, IL-5 levels in BAL Reduced mucus production Attenuated collagen deposition and smooth muscle cell activation |
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Theofani, E.; Xanthou, G. Autophagy: A Friend or Foe in Allergic Asthma? Int. J. Mol. Sci. 2021, 22, 6314. https://doi.org/10.3390/ijms22126314
Theofani E, Xanthou G. Autophagy: A Friend or Foe in Allergic Asthma? International Journal of Molecular Sciences. 2021; 22(12):6314. https://doi.org/10.3390/ijms22126314
Chicago/Turabian StyleTheofani, Efthymia, and Georgina Xanthou. 2021. "Autophagy: A Friend or Foe in Allergic Asthma?" International Journal of Molecular Sciences 22, no. 12: 6314. https://doi.org/10.3390/ijms22126314