Telocyte dynamics in psoriasis.

C.G Manole,Mihaela Gherghiceanu,Olga Simionescu

doi:10.1111/jcmm.12601

Abstract

The presence of telocytes (TCs) as distinct interstitial cells was previously documented in human dermis. TCs are interstitial cells completely different than dermal fibroblasts. TCs are interconnected in normal dermis in a 3D network and may be involved in skin homeostasis, remodelling, regeneration and repair. The number, distribution and ultrastructure of TCs were recently shown to be affected in systemic scleroderma. Psoriasis is a common inflammatory skin condition (estimated to affect about 0.1–11.8% of population), a keratinization disorder on a genetic background. In psoriasis, the dermis contribution to pathogenesis is frequently eclipsed by remarkable epidermal phenomena. Because of the particular distribution of TCs around blood vessels, we have investigated TCs in the dermis of patients with psoriasis vulgaris using immunohistochemistry (IHC), immunofluorescence (IF), and transmission electron microscopy (TEM). IHC and IF revealed that CD34/PDGFRα-positive TCs are present in human papillary dermis. More TCs were present in the dermis of uninvolved skin and treated skin than in psoriatic dermis. In uninvolved skin, TEM revealed TCs with typical ultrastructural features being involved in a 3D interstitial network in close vicinity to blood vessels in contact with immunoreactive cells in normal and treated skin. In contrast, the number of TCs was significantly decreased in psoriatic plaque. The remaining TCs demonstrated multiple degenerative features: apoptosis, membrane disintegration, cytoplasm fragmentation and nuclear extrusion. We also found changes in the phenotype of vascular smooth muscle cells in small blood vessels that lost the protective envelope formed by TCs. Therefore, impaired TCs could be a ‘missed’ trigger for the characteristic vascular pathology in psoriasis. Our data explain the mechanism of Auspitz’s sign, the most pathognomonic clinical sign of psoriasis vulgaris. This study offers new insights on the cellularity of psoriatic lesions and we suggest that TCs should be considered new cellular targets in forthcoming therapies.

Highlights

The cellularity of the dermis is perceived to be comprised of fibroblasts, endothelial cells, pericytes, dendritic cells (DCs), immune cells, macrophages, nerve endings, smooth muscle cells and the recently described telocytes (TCs) [1,2,3]
The biopsies taken from fully developed plaques exhibited the hyper-proliferation aspect of psoriasis: acanthosis with characteristic elongation of the rete ridges; hyperkeratosis with parakeratosis; and dilated and tortuous blood capillaries in the papillary dermis, with mild oedema, exhibiting chronic inflammatory infiltrate
Immunofluorescence showed that the density of TCs identified as CD34/ PDGFRa-positive cells was comparable in the dermis of uninvolved and treated skin but decreased in the lesional papillary dermis

Summary

Introduction

The cellularity of the dermis is perceived to be comprised of fibroblasts, endothelial cells, pericytes, dendritic cells (DCs), immune cells, macrophages, nerve endings, smooth muscle cells and the recently described telocytes (TCs) [1,2,3]. TCs are characterized by the presence of very long and slender moniliform cellular prolongations termed telopodes (Tps). The thickness of the thin segments of Tps (podomers) is comparable to that of collagen fibrils. The most advanced 3D microscopy technique (FIB-SEM tomography) revealed the spatial conformation of human dermal TCs and their Tps and extracellular vesicles [26]. Many studies have showed that TCs are completely different from fibroblasts in terms of cell culture [27, 28], ultrastructure [3, 24, 29, 30], miRNA imprint [31], gene profile [32,33,34] and proteomics [35]

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Conclusion