Autologous hematopoietic stem cell transplantation modulates epidermal-related inflammation/fibrosis mechanisms in systemic sclerosis patients

Abstract Background Autologous hematopoietic stem cell transplantation (auto-HSCT) has been shown to reduce cutaneous fibrosis and change dermal architecture in skin of systemic sclerosis (SSc) patients. However, its impact on the epidermis remains underexplored. Here, we examined whether auto-HSCT modulates epidermal inflammation and keratinocyte activity in SSc. Methods 29 patients with severe SSc who underwent auto-HSCT were retrospectively evaluated. Clinical data, skin biopsies, and serum samples were assessed before and at 6 months after transplantation. A healthy control group was included for comparison. Skin biopsies were qualitatively examined for epidermal thickness and expression of inflammatory/proliferation markers (S100A9, TNF-α, IL-1α, Ki-67) by immunohistochemistry. Serum molecules associated with inflammation and epidermal disturbances were quantified using Multiplex and ELISA assays. Serum samples from SSc patients and healthy controls were used to stimulate human HaCaT keratinocyte cell cultures, followed by quantification of pro-inflammatory CCL-5 cytokine in supernatants. Results There was significant improvement in the modified Rodnan Skin Scores (mRSS) after auto-HSCT. Epidermal thickness decreased after transplantation, although not reaching healthy control values. At baseline, serum levels of EGF, IL-1α, CCL-3, TNF-α, IFN-γ, IL-6, and IL-17 were higher in SSc patients than in healthy controls. Serum levels of TNF-α, IFN-γ, IL-6, and IL-17 did not change after auto-HSCT. Serum concentrations of CCL-5, CCL-2, IL-8, and HGF were not different from healthy controls and did not alter after transplantation. Conversely, EGF and IL-1α levels significantly decreased after auto-HSCT but remained higher than control levels. Only the serum levels of CCL-3 and CTGF decreased and normalized after auto-HSCT. Delta (Δ)mRSS and ΔIL-1α serum concentrations positively correlated after auto-HSCT. CCL-5 levels measured in supernatants from HaCaT cultures exposed to sera from SSc patients at baseline were not different than those exposed to sera from controls. However, when HaCat were exposed to post-transplantation serum, there was significant reduction in CCL-5 concentrations. Conclusions Auto-HSCT reduces epidermal thickness and inflammation in the skin of SSc patients, lowers serum markers of epithelial activation, and decreases CCL-5 release by stimulated keratinocytes. These findings suggest that, beyond resetting the immune system, auto-HSCT modulates epithelial disturbances associated with inflammation and fibrosis, supporting its therapeutic potential in this disease.