Abstract
Keloid is an aberrant scarring process of the skin, characterized by excessive extracellular matrix synthesis and deposition. The pathogenesis of this prevalent cutaneous disorder is not fully understood; however, a persistent inflammatory process is observed. To obtain more insight into this process, we analyzed lesional, perilesional and healthy tissue using multi-antigen-analysis (MAA) in conjunction with a data mining approach. Here, we demonstrate that monocyte-derived inflammatory dendritic cells (CD1a+, CD11c+, CD14+) and activated CD4+ T lymphocytes (CD45 RO+) dominated the immune infiltration in keloids while associating with fibroblasts. In perilesional tissue, precursor immune cells were dominant in the perivascular area, suggesting that they were attracted by an immune process, potentially in the lesional area. Supporting this hypothesis, only in keloid lesions, high levels of ADAM10/17 and Neprilysin (CD10) were observed in both fibroblasts and leukocytes. The spatial proximity of these two cell types, which could be confirmed by image analysis only in lesional tissue, could be a potential factor leading to the activation of fibroblasts. Our findings provide new insight into the pathogenesis of keloid formation and reveal metalloproteinases as a target for therapeutical intervention.
Highlights
The formation of scar tissue after injury constitutes a physiological healing process, reestablishing the functionality of the skin
Tissue may regenerate with or without scarring, or tissue fibrosis may lead to a pathological scar [1,2]
We have previously demonstrated that multi-antigen analysis (MAA) of tissue sections may provide new insights into the pathogenesis of diseases
Summary
The formation of scar tissue after injury constitutes a physiological healing process, reestablishing the functionality of the skin. Depending on the type of tissue and the type of injury, the wound healing process may vary. Tissue may regenerate with or without scarring, or tissue fibrosis may lead to a pathological scar [1,2]. The healing process becomes excessive, resulting in abnormal scar formation termed keloids (KD) [3]. Histopathological KD is characterized by a thick and flattened epidermis, increased cellularity and an abundance of extracellular matrix deposition in the dermis [4], resulting in pain, pruritus and aesthetic impairment [5]. Important biological functions, such as normal tissue growth, thermoregulation or normal range of movement, are impaired [6]
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