Abstract
Scars are generated in mature skin as a result of the normal repair process, but the replacement of normal tissue with scar tissue can lead to biomechanical and functional deficiencies in the skin as well as psychological and social issues for patients that negatively affect quality of life. Abnormal scars, such as hypertrophic scars and keloids, and cutaneous fibrosis that develops in diseases such as systemic sclerosis and graft-versus-host disease can be even more challenging for patients. There is a large body of literature suggesting that inflammation promotes the deposition of scar tissue by fibroblasts. Mast cells represent one inflammatory cell type in particular that has been implicated in skin scarring and fibrosis. Most published studies in this area support a pro-fibrotic role for mast cells in the skin, as many mast cell-derived mediators stimulate fibroblast activity and studies generally indicate higher numbers of mast cells and/or mast cell activation in scars and fibrotic skin. However, some studies in mast cell-deficient mice have suggested that these cells may not play a critical role in cutaneous scarring/fibrosis. Here, we will review the data for and against mast cells as key regulators of skin fibrosis and discuss scientific gaps in the field.
Highlights
When the skin is injured, the body initiates a wound-healing response
In contrast to the results described above, some studies have suggested that the density of tryptase-positive mast cells is similar in Hypertrophic scars (HTS) compared to normal surgical scars or normal skin [38,63,64,65], and one study suggested that there are reduced numbers of chymase-positive mast cells in HTS compared to normal skin [64]
An increase in the frequency of MCT cells compared to MCTC cells has been described in Systemic sclerosis (SSc) skin lesions [90], and other studies have shown that SSc is associated with an increase in the number of dermal mast cells expressing transforming growth factor (TGF)-β1/2 [88] or interleukin (IL)-17A [91]
Summary
When the skin is injured, the body initiates a wound-healing response. Depending on the tissue type and the severity of the injury, one of three general outcomes can result: regeneration of normal tissue without scarring, repair of the tissue with a scar, or fibrosis with excessive scar tissue production. The normal response to tissue damage in the skin is repair This well-characterized process begins with an inflammatory response during which resident inflammatory cells (e.g., mast cells and macrophages) become activated and circulating inflammatory cells (e.g., neutrophils and monocytes) are recruited. Mast cells have been suggested to play a role in each phase of the wound repair process, including the inflammatory, proliferative, and scar formation/remodeling phases. After injury, they contribute to inflammatory cell recruitment and help prevent infection, they can stimulate the proliferative phase by promoting keratinocyte/fibroblast activity as well as angiogenesis, and they can communicate with fibroblasts to influence scar formation [18,19,20]. This review will summarize the data supporting and opposing a critical role for mast cells in skin scarring and fibrosis from both human and animal studies, and will discuss open questions and future opportunities for research in this area
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