Differences in gene regulation by TLR3 and IPS-1 signaling in murine corneal epithelial cells

Scientific Reports · 7 authors, 3 centres

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TL;DR

This study used cultured corneal epithelial cells from TLR3 and IPS-1 knockout mice to show that these two signaling pathways, while both activated by the viral mimic polyI:C, regulate distinct sets of immune-related genes. The results suggest TLR3 and IPS-1 have complementary yet distinct functions in corneal innate immunity.

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This preclinical study investigated the differential gene regulation by TLR3 and IPS-1 pathways in murine corneal epithelial cells (CECs). Primary CECs from wild-type, TLR3-knockout, and IPS-1-knockout mice were stimulated with the dsRNA mimic polyI:C, and comprehensive gene expression analysis was performed. Results showed that antiviral response genes were upregulated in wild-type cells. Specific genes like Neurl3 and LIPG were dominantly regulated by TLR3, while IL-6 and IL-15 were dominantly regulated by IPS-1. Chemokines CCL5 and CXCL10, and genes OAS2, Slfn4, TRIM30α, and Gbp9 were complementarily regulated by both pathways. The study concludes that TLR3 and IPS-1 have distinct roles in the corneal innate immune response.

STUDY TYPE

other

SPECIALTY

ophthalmology

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AI pipeline

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100% · A

ORIGINAL PAPER

PMC10188512

Differences in gene regulation by TLR3 and IPS-1 signaling in murine corneal epithelial cells

Scientific Reports

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ABSTRACT

Toll-like receptor 3 (TLR3) and interferon-beta promoter stimulator-1 (IPS-1) are associated with antiviral responses to double-stranded RNA viruses and contribute to innate immunity. We previously reported that conjunctival epithelial cell (CEC) TLR3 and IPS-1 pathways respond to the common ligand polyinosinic:polycytidylic acid (polyI:C) to regulate different gene expression patterns as well as CD11c + cell migration in murine-model corneas. However, the differences in the functions and the roles of TLR3 and IPS-1 remain unclear. In this study, we investigated the differences of TLR3 or IPS-1-induced gene expression in corneal epithelial cells (CECs) in response to polyI:C stimulation using cultured murine primary CECs (mPCECs) derived from TLR3 and IPS-1 knockout mice via comprehensive analysis. The genes associated with viral responses were upregulated in the wild-type mice mPCECs after polyI:C stimulation. Among these genes, Neurl3, Irg1, and LIPG were dominantly regulated by TLR3, while interleukin (IL)-6 and IL-15 were dominantly regulated by IPS-1. CCL5, CXCL10, OAS2, Slfn4, TRIM30α, and Gbp9 were complementarily regulated by both TLR3 and IPS-1. Our findings suggest that CECs may contribute to immune responses and that TLR3 and IPS-1 possibly have different functions in the corneal innate immune response.

CITATION EXPORT

Seitaro Komai, Mayumi Ueta, Hiromi Nishigaki et al.. Differences in gene regulation by TLR3 and IPS-1 signaling in murine corneal epithelial cells. Scientific Reports. (2023). https://doi.org/10.1038/s41598-023-35144-1

AUTHORS

7 · 3 CENTRES

Seitaro Komai, Mayumi Ueta, Hiromi Nishigaki, Katsura Mizushima, Yuji Naito, Shigeru Kinoshita, Chie Sotozono

1grid.272458.e0000 0001 0667 4960Department of Ophthalmology, Kyoto Prefectural University of Medicine, 465 Kajii-Cho, Kamigyo-Ku, Kyoto, Japan
2grid.272458.e0000 0001 0667 4960Department of Human Immunology and Nutrition Science, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
3grid.272458.e0000 0001 0667 4960Department of Frontier Medical Science and Technology for Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan