Lacrimal Gland Epithelial Cells Shape Immune Responses through the Modulation of Inflammasomes and Lipid Metabolism

Authors

Vanessa Delcroix
Olivier Mauduit
Menglu Yang
Amrita Srivastava
Takeshi Umazume
Cintia S de Paiva
Valery I Shestopalov
Darlene A Dartt
Helen P Makarenkova

Publication Date

2-21-2023

Journal

International Journal of Molecular Sciences

DOI

10.3390/ijms24054309

PMID

36901740

PMCID

PMC10001612

PubMedCentral® Posted Date

2-21-2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Animals, Mice, Lacrimal Apparatus, Sjogren's Syndrome, Inflammasomes, Thrombospondin 1, Lipid Metabolism, Lipopolysaccharides, Nigericin, Mice, Inbred NOD, Mice, Inbred C57BL, Inflammation, Epithelial Cells, Immunity, lacrimal gland, inflammasome, lipid metabolism, Sjogren’s syndrome, dry eye, regeneration, acute inflammation, chronic inflammation

Abstract

Lacrimal gland inflammation triggers dry eye disease through impaired tear secretion by the epithelium. As aberrant inflammasome activation occurs in autoimmune disorders including Sjögren's syndrome, we analyzed the inflammasome pathway during acute and chronic inflammation and investigated its potential regulators. Bacterial infection was mimicked by the intraglandular injection of lipopolysaccharide (LPS) and nigericin, known to activate the NLRP3 inflammasome. Acute injury of the lacrimal gland was induced by interleukin (IL)-1α injection. Chronic inflammation was studied using two Sjögren's syndrome models: diseased