[The Journal of Experimental Medicine] Keratinocytes produce IL-17c to protect peripheral nervous sy
Despite frequent herpes simplex virus (HSV) reactivation, peripheral nerve destruction and sensory anesthesia are rare. We discovered that skin biopsies obtained during asymptomatic human HSV-2 reactivation exhibit a higher density of nerve fibers relative to biopsies during virological and clinical quiescence. We evaluated the effects of HSV infection on keratinocytes, the initial target of HSV replication, to better understand this observation. Keratinocytes produced IL-17c during HSV-2 reactivation, and IL-17RE, an IL-17c–specific receptor, was expressed on nerve fibers in human skin and sensory neurons in dorsal root ganglia. In ex vivo experiments, exogenous human IL-17c provided directional guidance and promoted neurite growth and branching in microfluidic devices. Exogenous murine IL-17c pretreatment reduced apoptosis in HSV-2–infected primary neurons. These results suggest that IL-17c is a neurotrophic cytokine that protects peripheral nerve systems during HSV reactivation. This mechanism could explain the lack of nerve damage from recurrent HSV infection and may provide insight to understanding and treating sensory peripheral neuropathies.
View ORCID ProfileTao Peng, R. Savanh Chanthaphavong, View ORCID ProfileSijie Sun, James A. Trigilio, Khamsone Phasouk, View ORCID ProfileLei Jin, Erik D. Layton, View ORCID ProfileAlvason Z. Li, Colin E. Correnti, Willem De van der Schueren, View ORCID ProfileJulio Vazquez, Diana R. O’Day, View ORCID ProfileIan A. Glass, David M. Knipe, View ORCID ProfileAnna Wald, View ORCID ProfileLawrence Corey, View ORCID ProfileJia Zhu
DOI: 10.1084/jem.20160581 | Published June 29, 2017