Int J Stem Cells.  2022 May;15(2):155-163. 10.15283/ijsc20210.

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

• Wang F
• Hou R
• Li J
• Zhao X
• Wang Q
• Zhang K
• Li X

• KMID: 2529787
• DOI: http://doi.org/10.15283/ijsc20210

Abstract

Background and Objectives
Mesenchymal stem cells (MSCs) have immunomodulatory function and participate in the pathogenesis of many immunoregulation-related diseases, including psoriasis. Previously, we found that MSCs from psoriatic lesions overexpress the proinflammatory microRNA, miR-155 and exhibit a decreased immunosuppressive capacity. But the origin of these aberrant characteristics is still not clear. To investigate whether inflammatory cytokines in serum and peripheral blood mononuclear cells (PBMCs) from psoriatic patients can regulate the expression patterns of immunoregulation-related cytokines and the immunoregulation function of MSCs.
Methods and Results
Normal dermal mesenchymal stem cells (nDMSCs) were treated with serum or PBMCs derived from patients with psoriasis or healthy donors. Expression of miR-155 and immunoregulation-related genes in each MSCs were measured using real-time PCR or western-blot. Meanwhile, the immunosuppressive capacity of DMSCs was evaluated by its inhibitory ability on proliferation of activated PBMCs. Compared to control serum, psoriatic serum significantly increased the expression levels of miR-155 (27.19±2.40 vs. 3.51±1.19, p<0.001), while decreased TAB2 expression (0.28±0.04 vs. 0.72±0.20, p<0.01) in DMSCs. Expression levels of immunoregulation-related genes such as PGE₂, IL-10, and TLR4 were also markedly down-regulated following the psoriatic serum treatment. Those DMSCs treated with healthy serum could inhibit PBMC proliferation, while those psoriatic serum-treated DMSCs could not inhibit PBMC proliferation effectively.
Conclusions
Psoriatic serum up-regulate the expression of miR-155, down-regulate the expression of immunoregulation- related genes (PGE₂, IL-10, and TLR4) in DMSCs, and along with the inhibition of the immunosuppressive function of MSCs.

Keyword

Mesenchymal stem cell; Psoriasis; Cytokine; Immunoregulatory

Figure

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  Fig. 1 Psoriatic serum up-regulate miR-155, while inhibiting TAB2 expression in DMSCs. (a) Cell morphology of untreated DMSCs, PS-DMSCs, PMNC-DMSCs (scale bar=100 μm); (b) The mRNA levels of miR-155 were up-regulated and TAB2 were down-regulated in PS-DMSCs and Cy-DMSCs than in HS-DMSCs; (c, d) The protein levels of TAB2 were down-regulated in PS-DMSCs and Cy-DMSCs than in HS-DMSCs; (e) The mRNA levels of miR-155 and TAB2 were similar between PMNC-DMSCs and HMNC-DMSCs. *Represents the difference between each group and nDMSCs. *p<0.05, **p<0.01, ***p<0.001, N=6. Abbreviation: nDMSCs: untreated DMSCs; HS-DMSCs: DMSCs treated with normal serum; PS-DMSCs: DMSCs treated with psoriatic serum; HMNC-DMSCs: DMSCs treated with normal PBMCs; PMNC-DMSCs: DMSCs treated with psoriatic PBMCs; Cy-DMSCs: DMSCs treated with cytokines (TNF-α and IL-1β).

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  Fig. 2 Psoriatic serum suppress the mRNA expression of immunoregula-tion-related genes in DMSCs. (a) Expression levels of mRNA for IL-10, PGE2 and TLR4 were down-regulated in PS-DMSCs and Cy-DMSCs than in HS-DMSCs; (b) The mRNA levels of IL-10, PGE2, TLR4 were similar between PMNC-DMSCs and HMNC-DMSCs; (c, d) The protein levels of IL-10 and TLR4 were down-regulated in PS-DMSCs and Cy-DMSCs than in HS-DMSCs. *Re-presents the difference between each group and nDMSCs. *p<0.05, **p< 0.01, ***p<0.001, N=6. Abbrevia-tion: nDMSCs: untreated DMSCs; HS-DMSCs: DMSCs treated with normal serum; PS-DMSCs: DMSCs treated with psoriatic serum; HMNC-DMSCs: DMSCs treated with normal PBMCs; PMNC-DMSCs: DMSCs treated with psoriatic PBMCs; Cy-DMSCs: DMSCs treated with cytokines (TNF-α and IL-1β).

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  Fig. 3 Psoriatic serum inhibit the immunosuppression of DMSCs. (a) Morphology of PBMCs cultured alone and co-cultured with either HS-DMSCs or PS-DMSCs or Cy-DMSCs for 3 days; (b) Proliferation of PBMCs cultured alone and co-cultured with either HS-DMSCs or PS-DMSCs or Cy-DMSCs for 3 days, *Represents the difference between each group and nDMSCs, ***p<0.001; (c) Expression levels of mRNA for IL-17A, IL-23, and IL-8 in PBMCs cultured alone and co-cultured with either HS-DMSCs or PS-DMSCs or Cy-DMSCs, a represents p<0.05 vs. nDMSCs, b represents p<0.001 vs. nDMSCs, c represents p<0.05 vs. HS-DMSCs, d represents p<0.001 vs. HS-DMSCs, ***p<0.001, N=6. Abbreviation: nDMSCs＋PBMCs: PBMCs co-cultured with nDMSCs (untreated DMSCs); HS-DMSCs＋PBMCs: PBMCs co-cultured with HS-DMSCs (DMSCs treated with normal serum); PS-DMSCs＋PBMCs: PBMCs co-cultured with PS-DMSCs (DMSCs treated with psoriatic serum); Cy-DMSCs＋PBMCs: PBMCs co-cultured with Cy-DMSCs (DMSCs treated with cytokines [TNF-α and IL-1β]); PBMCs: PBMCs cultured alone.

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  Fig. 4 The effect of psoriatic serum on dermal mesenchymal stem cells. The increased TNF-α and IL-1β in the psoriatic serum up-regulate the expression of miR-155 and down-regulate the expression of TAB2 in DMSCs, along with the down-regulation of expression of PGE2, IL-10 and TLR4 and decreasing immuno-suppressive ability of DMSCs. As a result, the proliferation and expression of inflammatory cytokines IL-17A, IL-23, IL-8 of PBMCs were increased, which in turn, further aggravate cutaneous inflammation.

Reference

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