Trauma of Peripheral Innervation Impairs Content of Epidermal Langerhans Cells

Abstract

Langerhans cells represent the first immune cells that sense the entry of external molecules and microorganisms at the epithelial level in the skin. In this pilot case-study, we evaluated Langerhans cells density and progression of epidermal atrophy in permanent spinal cord injury (SCI) patients suffering with either lower motor neuron lesions (LMNSCI) or upper motor neuron lesions (UMNSCI), both submitted to surface electrical stimulation. Skin biopsies harvested from both legs were analyzed before and after 2 years of home-based Functional Electrical Stimulation for denervated degenerating muscles (DDM) delivered at home (h-bFES) by large anatomically shaped surface electrodes placed on the skin of the anterior thigh in the cases of LMNSCI patients or by neuromuscular electrical stimulation (NMES) for innervated muscles in the cases of UMNSCI persons. Using quantitative histology, we analyzed epidermal thickness and flattening and content of Langerhans cells. Linear regression analyses show that epidermal atrophy worsens with increasing years of LMNSCI and that 2 years of skin electrostimulation reverses skin changes, producing a significant recovery of epidermis thickness, but not changes in Langerhans cells density. In UMNSCI, we did not observe any statistically significant changes of the epidermis and of its content of Langerhans cells, but while the epidermal thickness is similar to that of first year-LMNSCI, the content of Langerhans cells is almost twice, suggesting that the LMNSCI induces an early decrease of immunoprotection that lasts at least 10 years. All together, these are original clinically relevant results suggesting a possible immuno-repression in epidermis of the permanently denervated patients.

Keywords: Langerhans cells; electrical stimulation; epidermis atrophy; lower or upper motor neuron injury; skin biopsy; spinal cord injury.

Figure 1

Histological sections of 5 µm thickness were collected and stained by (A) standard Hematoxilin-Eosin (H-E) stain protocol and (B) with a standard immunohistochemical procedure to analyze CD1a, a specific marker of Langerhans Cells (LCs); * = the distance between the outermost surface of the epidermis (excluding the stratum corneum) and the dermo–epidermal junction; ** = outline of total area of epidermis.

Figure 2

Multiple regression analysis on LMNSCI before the h-bFES, indicating a moderate (R < 0.7) but significant (p < 0.01, see Table 2) change of epidermis thickness with both age (A) and time from injury (B) and change of Interdigitation index (INT index) with both age (C) and time from injury (D). The indicated Johnson’s weight estimates the relative impact of each of the two factors on the multiple correlation factors.

Figure 3

Quantitative analysis of CD1a-immunostained epidermal sections from UMNSCI patients before (pre) and after (post) 2 years of NMES. IR% represents the immunoreactive area occupied in the epidermis by Langerhans cells, while n/mm² is their numerical density. Data are mean ± SEM; * = p < 0.05, paired t-test.

Figure 4

Langerhans cells (CD1a positive) in UMNSCI vs LMNSCI: Quantitation in immunostained epidermal sections of CD1a before + after (Pre + Post) 2 years of NMES on UMNSCI and before (pre) in LMNSCI. IR% is the percentage of immunoreactivity for CD1a; n/mm² is the number of LC bodies per square millimeter of epidermis; data are mean ± SEM; statistical significance at p < 0.05 (*) p < 0.0001 (**), unpaired t test.