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TGF- Regulates TLR Expression and Function on Epidermal Keratinocytes¹

Lloyd S. Miller^*,, Ole E. Sørensen, Philip T. Liu, H. Ray Jalian^*, Deborah Eshtiaghpour^*, Behnaz E. Behmanesh^*, Woosin Chung^*, Timothy D. Starner, Jenny Kim^*,, Peter A. Sieling^*, Tomas Ganz and Robert L. Modlin^2,*,

^* Division of Dermatology, Department of Microbiology, Immunology, and Molecular Genetics, and Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095; Department of Pediatrics, University of Iowa Hospitals and Clinics, Iowa City, IA 52242

The expression of TLRs on epithelial cells provides a first line of defense against invading pathogens. We investigated the regulated expression and function of TLR5 and TLR9 on human keratinocytes, because we found by immunohistochemistry that these TLRs are expressed in distinct layers of the epidermis. We found that TGF-, a growth and differentiation factor that is present during wound healing and in psoriasis, increased the expression of both TLR5 and TLR9 on keratinocytes. In addition, TGF- regulated the function of TLR5 and TLR9, because activation with their respective ligands enhanced the production of IL-8 and human -defensins. These findings provide evidence that TGF- up-regulates TLR expression and function, augmenting host defense mechanisms at epithelial surfaces.

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