title: Langerhans cells regulate cutaneous innervation density and mechanical sensitivity in mouse footpad.
abstract: Langerhans cells are epidermal dendritic cells responsible for antigen presentation during an immune response. Langerhans cells associate intimately with epidermal sensory axons. While there is evidence that Langerhans cells may produce neurotrophic factors, a role in regulating cutaneous innervation has not been established. We used genetically engineered mice in which the diphtheria toxin (DT) receptor is targeted to Langerhans cells (Lang-DTR mice) to assess sensory axon-dendritic cell interactions. Diphtheria toxin administration to wild type mice did not affect epidermal structure, Langerhans cell content, or innervation density. A DT administration regimen supramaximal for completely ablating epidermal Langerhans cells in Lang-DTR mice reduced PGP 9.5-immunoreactive total innervation and calcitonin gene related peptide-immunoreactive peptidergic nociceptor innervation. Quantitative real-time polymerase chain reaction showed that epidermal gene expression of brain derived neurotrophic factor was unchanged, but nerve growth factor and glial cell line-derived neurotrophic factor mRNAs were reduced. Behavioral testing showed that, while thermal sensitivity was unaffected, mice depleted of Langerhans cells displayed mechanical hypersensitivity. These findings provide evidence that Langerhans cells play an important role in determining cutaneous sensory innervation density and mechanical sensitivity. This may involve alterations in neurotrophin production by Langerhans or other epidermal cells, which in turn may affect mechanical sensitivity directly or as a result of neuropathic changes.
authors: Institute for Neurological Discoveries, University of Kansas Medical Center, Kansas City, KS 66160, USA; Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA; Kansas Intellectual and Developmental Disabilities Research Center, University of Kansas Medical Center, Kansas City, KS 66160, USA.
authors: Argenia L N
authors: AL
authors: Doss
authors: Institute for Neurological Discoveries, University of Kansas Medical Center, Kansas City, KS 66160, USA; Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA; Kansas Intellectual and Developmental Disabilities Research Center, University of Kansas Medical Center, Kansas City, KS 66160, USA. Electronic address: psmith@kumc.edu.
authors: Peter G
authors: PG
authors: Smith
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D004817:Epidermis / Q000294:innervation* / Q000378:metabolism*; D005528:Foot / Q000294:innervation* / Q000502:physiology; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism; D006930:Hyperalgesia / Q000378:metabolism; D007801:Langerhans Cells / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009412:Nerve Fibers / Q000378:metabolism*; D020932:Nerve Growth Factor / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D051100:Glial Cell Line-Derived Neurotrophic Factor; D020932:Nerve Growth Factor
keywords: Behavioral testing; Dendritic cells; Neural–immune interactions; Neurotrophic factors; Sensory axons