Langerhans cells regulate cutaneous innervation density and mechanical sensitivity in mouse footpad

Area of Science:

• Immunology
• Neuroscience
• Dermatology

Background:

• Langerhans cells are epidermal dendritic cells crucial for immune responses.
• Their intimate association with sensory axons suggests a role in regulating cutaneous innervation.
• The precise function of Langerhans cells in sensory nerve regulation remains unclear.

Purpose of the Study:

• To investigate the role of Langerhans cells in regulating cutaneous sensory innervation and function.
• To determine if Langerhans cells influence neurotrophic factor expression in the epidermis.
• To assess the impact of Langerhans cell depletion on sensory behaviors.

Main Methods:

• Utilized genetically engineered Lang-DTR mice for targeted Langerhans cell ablation using diphtheria toxin (DT).
• Assessed epidermal structure, Langerhans cell density, and sensory innervation (PGP 9.5, CGRP) via immunohistochemistry.
• Quantified epidermal gene expression of neurotrophic factors (BDNF, NGF, GDNF) using qRT-PCR.
• Evaluated thermal and mechanical sensitivity through behavioral testing.

Main Results:

• DT administration in Lang-DTR mice effectively ablated epidermal Langerhans cells without affecting wild-type mice.
• Langerhans cell depletion significantly reduced total and peptidergic nociceptor innervation density.
• Epidermal NGF and GDNF mRNA levels decreased, while BDNF remained unchanged.
• Mice lacking Langerhans cells exhibited mechanical hypersensitivity but normal thermal sensitivity.

Conclusions:

• Langerhans cells play a critical role in maintaining cutaneous sensory innervation density.
• These cells influence mechanical sensitivity, potentially via neurotrophin production.
• Findings suggest a significant interaction between immune cells and sensory nerves in the skin.