Psoriatic Serum Induce an Abnormal Inflammatory Phenotype and a Decreased Immunosuppressive Function of Mesenchymal

Fangdi Wang1, Ruixia Hou1, Junqin Li1

  • 1Shanxi Key Laboratory of Stem Cells for Immunological Dermatosis, Institute of Dermatology, Taiyuan Central Hospital of Shanxi Medical University, Taiyuan, China.

Abstract

Insights

Psoriatic serum increases pro-inflammatory miR-155 and decreases immunosuppressive factors in mesenchymal stem cells (MSCs). This impairs their ability to regulate immune responses, contributing to psoriasis pathogenesis.

Area of Science:

  • Immunology
  • Stem Cell Biology
  • Dermatology

Background:

  • Mesenchymal stem cells (MSCs) possess immunomodulatory functions crucial in regulating immune responses.
  • Dysfunctional MSCs are implicated in immune-related diseases like psoriasis, with psoriatic MSCs showing altered miR-155 expression and reduced immunosuppressive capacity.
  • The factors contributing to these aberrant MSC characteristics in psoriasis remain unclear.

Purpose of the Study:

  • To investigate the impact of inflammatory cytokines in psoriatic serum and peripheral blood mononuclear cells (PBMCs) on MSCs.
  • To determine if these factors modulate the expression of immunoregulatory genes and the immunosuppressive function of MSCs.

Main Methods:

  • Normal dermal MSCs (nDMSCs) were incubated with serum or PBMCs from psoriasis patients or healthy donors.
  • Quantitative real-time PCR and western blot were used to assess miR-155 and immunoregulatory gene expression in MSCs.
  • The immunosuppressive capacity of treated MSCs was evaluated by their effect on activated PBMC proliferation.

Main Results:

  • Psoriatic serum significantly upregulated miR-155 expression in nDMSCs compared to control serum (27.19±2.40 vs. 3.51±1.19, p<0.001).
  • Psoriatic serum treatment led to decreased expression of TAB2, PGE2, IL-10, and TLR4 in nDMSCs.
  • MSCs treated with psoriatic serum exhibited a diminished ability to suppress PBMC proliferation compared to those treated with healthy serum.

Conclusions:

  • Psoriatic serum induces overexpression of miR-155 in dermal MSCs.
  • Psoriatic serum downregulates key immunoregulatory genes (PGE2, IL-10, TLR4) within MSCs.
  • These alterations collectively inhibit the immunosuppressive function of MSCs, potentially contributing to psoriasis pathogenesis.

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