# Interplay Between Langerhans Cells and Sensory Neurons: Impact on Wound Healing and Nociception Following Burn Injuries

> **NIH NIH R01** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2024 · $330,025

## Abstract

PROJECT SUMMARY
 Effective wound care is of paramount importance for individuals who have sustained burn injuries.
Wound healing is intricately associated with the sensations of itching and pain, which can significantly impact a
patient's quality of life. Following a burn injury, monocyte-derived Langerhans cells (LCs) are mobilized from
the bone marrow and recruited to the epidermal layer, potentially playing a pivotal role in the wound healing
process. Furthermore, the sensations of itch and pain are largely mediated by the free nerve endings of
nociceptive sensory neurons, often found in close proximity to resident LCs within the epidermis. However, our
comprehension of how LCs modulate wound healing, itching, and pain remains notably limited, primarily due to
the absence of established methods for selectively manipulating LC activity. Here, we hypothesize that
distinct subsets of LCs mediate wound healing, itch, and pain after burn injury. To test this hypothesis, we
have successfully applied optogenetics to directly control the activity of LCs by establishing a mouse line
that selectively expresses light-sensitive cation channels (ChR2) in LCs. We have also successfully
applied chemogenetics to directly control the activity of LCs by establishing a mouse line that selectively
expresses Gq- or Gi-biased Designer Receptors Exclusively Activated by Designer Drugs (Gq- or Gi-
DREADD) in LCs. The long-term goal of this application is to advance our understanding of the molecular
mechanisms behind wound healing, itch, and pain after burn injury regulated by LC-sensory neuron
interaction and to offer innovative ways to treat these conditions by targeting LCs. Aim 1 will determine the
role of LC-sensory neuron interaction in wound healing using hematopoietic chimeras in which monocyte-
derived LCs selectively express Gq- or Gi-DREADD and transgenic mice in which sensory neurons
selectively express Gq- or Gi-DREADD. Aim 2 will determine the contribution of LCs to postburn itch and
pain using hematopoietic chimeras in which resident LCs selectively express ChR2 or Gi-DREADD, and in
vitro calcium imaging from LCs. Aim 3 will genetically define the heterogeneous population of LCs involved
in wound healing or nociception after burn injury using single-cell RNAseq. This proposal will help us to
understand completely new roles for LCs and how they may regulate wound healing and wound-related
itch and pain after burn injury. The successful completion of this proposal would provide a unique
approach to treating wound healing, wound-related itch, and pain after burn injury by targeting distinct
subsets of LCs.

## Key facts

- **NIH application ID:** 10943495
- **Project number:** 1R01GM155523-01
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** Tasuku Akiyama
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $330,025
- **Award type:** 1
- **Project period:** 2024-09-15 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10943495

## Citation

> US National Institutes of Health, RePORTER application 10943495, Interplay Between Langerhans Cells and Sensory Neurons: Impact on Wound Healing and Nociception Following Burn Injuries (1R01GM155523-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10943495. Licensed CC0.

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