Dermal Dendritic Cell Population and Blood Vessels Are Diminished in the Skin of Systemic Sclerosis Patients

Abstract

Recent studies have suggested that the number of dermal dendritic cells is altered in the skin of patients with scleroderma and that these cells may have an important role in the pathogenesis of this disease. There is also a belief that insufficient blood flow to the affected organs may also be responsible for the disease. Our aim was to quantify CD34+ cells, factor XIIIa cells, and blood vessels in the skin of patients with systemic sclerosis and to correlate these data with fibrosis degree and duration of disease. Paraffin-embedded skin sections from patients with systemic sclerosis and from healthy subjects were immunolabelled with antibodies against CD34+ and factor XIIIa. Cells and blood vessels were quantified in the papillary and reticular dermis. Both, the number of CD34+ cells and factor XIIIa cells in the skin of patients with systemic sclerosis were reduced. The reduction of these cell types preceded the appearance of intense fibrosis, suggesting that fibrosis is not responsible of this phenomenon. Blood vessel volume and surface density were also reduced in the skin of systemic sclerosis patients. This reduction was also noted early in the evolution of the disease. Our results suggest that CD34+ cells and factor XIIIa cells may contribute to normal regulation of extracellular matrix assembly. We confirmed the observation that capillary density is diminished in scleroderma skin.

CD34 stromal expression is inversely proportional to smooth muscle actin expression and extent of morphea

“…Although pathophysiology of scleroderma is still unclear, fibrosis is believed to be the clinical hallmark of the disease and plays a critical role in causing tissue damage in scleroderma. [3][4][5] Change in the distribution of DDCs was reported in scleroderma, particularly CD34+ DDCs [3][4][5][6][7][8][9] and factor XIIIa+ (FXIIIa) DDCs. Upon tissue injury, fibroblasts differentiate into activated fibroblasts or myofibroblasts, which express smooth muscle actin (SMA) unlike fibroblasts, and they participate in wound-healing process.…”

“…1 Fibroblasts are known as the key effectors to fibrosis. [3][4][5]7,8,10 Their exact role or origin After the process, myofibroblasts are normally lost from the site of injury, whereas in fibrotic pathologies such as scleroderma they remain.…”

“…7 Few studies have described their reduction in scleroderma. CD34+ DDCs are thought to be involved in wound healing of normal skin, 2 and they are predominantly located in the reticular and periadnexal dermis.…”

“…CD34+ DDCs are thought to be involved in wound healing of normal skin, 2 and they are predominantly located in the reticular and periadnexal dermis. 7,13 Previous studies have shown variable results in scleroderma: some authors found FXIIIa+ DDCs to increase in morphea (localized scleroderma), 4,5,8,10 others found them to decrease in systemic scleroderma. [3][4][5][6]8,9 FXIIIa+ DDCs are thought to inhibit collagen accumulation in skin, 11,12 and they are mainly located in the papillary dermis.…”

Factor XIII Subunit A in the Skin: Applications in Diagnosis and Treatment

“…Interestingly, preceding the appearance of intense fibrosis, a reduction was also found in FXIII-A-positive cell numbers. This finding pointed to the presence of FXIII-A-positive cells that varied according to different stages of disease pathogenesis [77] and the fact that these cells might be important in fibrosis by crosslinking the newly formed ECM also found in scleroderma [66]. …”