Abstract
BackgroundPsoriasis is a chronic and systemic, immune-mediated, inflammatory disease. Mesenchymal stem cells have effects on the inflammatory microenvironment, including regulating the proliferation, differentiation, recruitment, and migration of immunocytes.MethodsTo investigate whether dermal mesenchymal stem cells (DMSCs) may act on migration of immunocytes in psoriasis patients, 22 patients with psoriasis and 22 matching healthy controls (age and sex in this study) were recruited. Seven migration-associated genes including chemokine like receptor-1 (CMKLR-1), collagen type VIII alpha1 (COL8A-1), neuropilin and tolloid-like 2 (NETO-2), nik-related kinase (NRK), secreted frizzled-related protein (SFRP), sulfate 6-O-endosulfatase 2 (SULF-2), and synaptotagmin-like protein 2 (SYTL-2) were analyzed by quantitative real-time reverse transcription PCR and western blot. Peripheral blood-derived mononuclear cells (PBMCs) migration to MSCs was measured using a Thanswell chamber system.ResultsWe observed the upregulation of CMKLR-1, COL8A-1, NETO-2, NRK, SYTL-2, and SULF-2 in dermal mesenchymal stem cells derived from patients with psoriasis at both mRNA and protein level, however, a significant downregulation of SFRP-2 between two groups. By contrast, there were no significant between-group differences at the mRNA and protein expression level of NETO-2 and SULF-2. The migration assay showed that in vitro the normal PBMC migration to psoriatic DMSC group was a 6.3 ± 0.7-fold increase compared with the control group.ConclusionsThe results may suggest a potential pathogenetic involvement of DMSCs on migration of monocytes in psoriasis. Immune responses are regulated at the level of DMSCs, which probably represent the cells primarily involved in the “psoriatic march.”
Highlights
Psoriasis is a chronic and systemic, immune-mediated, inflammatory disease
In one of earlier studies, we found that dermal mesenchymal stem cells (DMSCs) derived from patients with psoriasis had an imbalance in cytokine secretion, including the increased levels of epidermal growth factor (EGF), stem cell factor (SCF), and interleukin-1 (IL-1) as well as the decreased levels of basic fibroblast growth factor, IL-3, IL-6, IL-8, and hepatocyte growth factor (HGF) [8]
We observed significant increases in protein expression of chemokine like receptor-1 (CMKLR-1), Collagen type VIII alpha1 (COL8A-1), nik-related kinase (NRK), and synaptotagmin-like protein 2 (SYTL-2) in DMSCs from patients with psoriasis compared with those from healthy donors, whereas the expression level of secreted frizzled-related protein (SFRP)-2 was obviously decreased (Fig. 3a, b)
Summary
Psoriasis is a chronic and systemic, immune-mediated, inflammatory disease. Mesenchymal stem cells have effects on the inflammatory microenvironment, including regulating the proliferation, differentiation, recruitment, and migration of immunocytes. Psoriasis is one of the most common immune-mediated chronic inflammatory skin disorders. Niu et al Stem Cell Research & Therapy (2019) 10:54 and clinical evidence has shown that systemic infusion of MSCs has significant immunosuppressive effects on the treatment of a variety of inflammatory and autoimmune diseases by inhibiting the proliferation and function of immune cells, including T cells, B cells, NK cells, monocytes/ macrophages, dendritic cells (DCs), and neutrophils [4]. MSCs may modulate the capability of activated lymphocytes by selectively acting on specific adhesion molecules and chemokine receptors involved in the extravasations and migration of activated T cells
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