TLR3 activation mediates partial epithelial-to-mesenchymal transition in human keratinocytes
TLR3 is expressed in human skin and keratinocytes, and given its varied role in skin inflammation, development, and regeneration, we sought to determine the cellular response in normal human keratinocytes to TLR3 activation. We investigated this mechanism by treating primary human keratinocytes with both UVB, an endogenous and physiologic TLR3 activator, and poly(I:C), a synthetic and selective TLR3 ligand. TLR3 activation with either UVB or poly(I:C) altered keratinocyte morphology, coinciding with the key features of epithelial-to-mesenchymal transition: increased epithelial-to-mesenchymal transition gene expression, enhanced migration, and increased invasion properties. These results confirm and extend previous studies demonstrating that in addition to its classical role in the innate immune response, TLR3 signaling also regulates stem cell-like properties and developmental programs.
Authors
- Lisa M. Shantz (ORCID: https://orcid.org/0000-0001-8814-4022)
- Mackenzie L. Sennett (ORCID: https://orcid.org/0000-0003-4964-3835)
- Robert P. Feehan (ORCID: https://orcid.org/0000-0001-5368-1872)
- Elizabeth M. Billingsley
- Amanda M. Nelson (ORCID: https://orcid.org/0000-0001-6375-8706)
- Zhaoyuan Cong (ORCID: https://orcid.org/0000-0001-9895-2912)
- Carson A. Wills (ORCID: https://orcid.org/0000-0003-0356-3071)
- Andreá Schneider (ORCID: https://orcid.org/0000-0002-9725-4634)
- C. Garner (ORCID: https://orcid.org/0000-0002-0772-6483)
- Alexandra F. Flamm (ORCID: https://orcid.org/0000-0001-6719-9411)
Institutions
- Penn State Milton S. Hershey Medical Center (US)
Publication Details
- Journal
- Life Science Alliance
- Published
- 2024-09-30
- DOI
- https://doi.org/10.26508/lsa.202402777
- Citations
- 2
- Primary Topic
- Immune Response and Inflammation
- Type
- article
- Field-Weighted Citation Impact
- 0.48
Funders
- American Skin Association
- University of Pennsylvania
- Pennsylvania State University
- National Institutes of Health
- Penn State College of Medicine
- National Institute of Environmental Health Sciences
- National Institute of Arthritis and Musculoskeletal and Skin Diseases