Lacrimal Gland Epithelial Cells Shape Immune Responses through the Modulation of Inflammasomes and Lipid Metabolism
Abstract
:1. Introduction
2. Methods
2.1. Mice
2.2. Induction of Inflammasome Formation with Lipopolysaccharide and Nigericin
2.3. LG Acute Injury
2.4. Frozen Section Preparation and Immunostaining
2.5. Western Blotting Analysis
2.6. qRT-PCR
2.7. RNA-Sequencing (RNA-seq) Data Analysis
2.8. Statistical Analysis
3. Results
3.1. Epithelial Cells Can Sense Microbial/Sterile Inflammatory Stimuli
3.2. Inflammasome Activation during Chronic Inflammation
3.3. Acute Injury and Chronic Inflammation Upregulate Several Types of Inflammasomes
3.4. The Resolution of Inflammation and LG Regeneration following Acute Injury Is Concomitant with the Activation of Lipid Metabolism
3.5. Lipid Metabolism Is Altered in Chronically Inflamed LG of NOD.H2b Mice
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Ethics Approval and Consent to Participate
Abbreviations
ACACB | Acetyl-CoA Carboxylase Beta |
ACSS2 | Acyl-CoA Synthetase Short Chain Family Member 2 |
ADDE | Aqueous deficiency dry eye |
AIM2 | Absent in melanoma 2 |
ALDH3B2 | Aldehyde Dehydrogenase 3 Family Member B2 |
ANGT | Angiotensinogen |
ASC | Apoptosis-associated speck-like protein containing a CARD |
ATP | Adenosine triphosphate |
CASP | Caspase |
CoA | Coenzyme A |
DAG | Diacylglycerol |
DEG | Differentially expressed gene |
DGKγ | Diacylglycerol Kinase Gamma |
E-CAD | E-Cadherin |
FA | Fatty acid |
GBP | Guanylate-binding proteins |
GSDMD | Gasdermin D |
HMGCR | 3-Hydroxy-3-Methylglutaryl-CoA Reductase |
IFI204 | Interferon-activable protein 204 |
IFN | Interferon |
IL | Interleukin |
LG | Lacrimal gland |
LPS | Lipopolysaccharide |
M | Months old |
MEC | Myoepithelial cell |
MyD88 | Myeloid differentiation primary response 88 |
NFκB | Nuclear factor kappa B |
NLRP | nucleotide-binding oligomerization domain, leucine-rich repeat and Pyrin domain containing Proteins |
PA | Phosphatidic acid |
PANX1 | Pannexin-1 |
PPARα | Peroxisome proliferator-activated receptor alpha |
pSS | Primary Sjögren’s syndrome |
PUFA | Polyunsaturated fatty acid |
PYHIN | Pyrin and HIN domain-containing protein |
R26 | Rosa26 locus |
RXRα | Retinoid X receptor alpha |
SQLE | Squalene Epoxidase |
SREBP1 | Sterol regulatory element-binding protein 1 |
SS | Sjögren’s syndrome |
SYK | Spleen Associated Tyrosine Kinase |
TCA | Tricarboxylic acid |
TLR | Toll-like receptor |
TSP-1 | Thrombospondin-1 |
VLCFA | Very long-chain fatty acid |
α-SMA | Alpha Smooth Muscle Actin |
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Target | Primer Sequence |
---|---|
Nlrp3 | Forward: 5′-AGAAGAGACCACGGCAGAAG-3′ |
Reverse: 5′-CCTTGGACCAGGTTCAGTGT-3′ | |
Nlrc4 | Forward: 5′-CTTGGCCAGGAGAGCCTTG-3′ |
Reverse: 5′-GGGCTCGTCTGTTGTTCCTT-3′ | |
Aim2 | Forward: 5′-GATTCAAAGTGCAGGTGCGG-3′ |
Reverse: 5′-TCTGAGGCTTAGCTTGAGGAC-3′ | |
Casp1 | Forward: 5′-GCGAAGCATACTTTCAGTTTC-3′ |
Reverse: 5′-TCTCCTTCAGGACCTTGTCG-3′ | |
Casp4(11) | Forward: 5′-AGGAGCCCACTCCTACAGAG-3′ |
Reverse: 5′-AAGGTTGCCCGATCAATGGT-3′ | |
Actb | Forward: 5′-AGAGGGAAATCGTGCGTGAC-3′ |
Reverse: 5′-CAATAGTGATGACCTGGCCGT-3′ | |
Gapdh | Forward: 5′-CGTCCCGTAGACAAAATG GT-3′ |
Reverse: 5′-TTGATGGCAACAATCTCC AC-3′ |
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© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Delcroix, V.; Mauduit, O.; Yang, M.; Srivastava, A.; Umazume, T.; de Paiva, C.S.; Shestopalov, V.I.; Dartt, D.A.; Makarenkova, H.P. Lacrimal Gland Epithelial Cells Shape Immune Responses through the Modulation of Inflammasomes and Lipid Metabolism. Int. J. Mol. Sci. 2023, 24, 4309. https://doi.org/10.3390/ijms24054309
Delcroix V, Mauduit O, Yang M, Srivastava A, Umazume T, de Paiva CS, Shestopalov VI, Dartt DA, Makarenkova HP. Lacrimal Gland Epithelial Cells Shape Immune Responses through the Modulation of Inflammasomes and Lipid Metabolism. International Journal of Molecular Sciences. 2023; 24(5):4309. https://doi.org/10.3390/ijms24054309
Chicago/Turabian StyleDelcroix, Vanessa, Olivier Mauduit, Menglu Yang, Amrita Srivastava, Takeshi Umazume, Cintia S. de Paiva, Valery I. Shestopalov, Darlene A. Dartt, and Helen P. Makarenkova. 2023. "Lacrimal Gland Epithelial Cells Shape Immune Responses through the Modulation of Inflammasomes and Lipid Metabolism" International Journal of Molecular Sciences 24, no. 5: 4309. https://doi.org/10.3390/ijms24054309