Skin innervation has been considered to subserve sensory perception on
ly, but several lines of evidence suggest that there are 'effector' in
fluences of skin innervation on the immune system and keratotinocytes.
In this study, we transected the sciatic nerves of rats and examined
the effects of denervation on the epidermis. In normal skin, the epide
rmis was densely innervated by fine axons that were immunostained with
several axonal markers, including neuronal ubiquitin carboxyl termina
l hydrolase (protein gene product 9.5). All of the epidermal axons in
the regions innervated by sciatic nerve disappeared within 24-48 h aft
er transection of sciatic nerve, and remained absent as long as subseq
uent reinnervation by regenerating axonal sprouts was prevented. Dener
vation produced changes in both the keratinocytes and the Langerhans c
elis, the bone marrow-derived antigen-presenting cells of the epidermi
s. The thickness of epidermis decreased within 7 days. By 48 h after t
ransection the Langerhans cells and their dendritic processes became i
ntensely immunoreactive for protein gene product. Protein gene product
9.5 expression on Langerhans cells remained prominent as long as skin
was denervated, but disappeared with reinnervation. By reverse transc
ription-polymerase chain reaction, we demonstrated the presence of the
transcripts for protein gene product 9.5 in epidermis, consistent wit
h the synthesis of the protein by the Langerhans cells. We conclude th
at epidermal sensory fibres have novel influences on both keratinocyte
s and Langerhans cells of the epidermis.