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Updated: Jan 8, 2026

Development of Stem Cell-derived Antigen-specific Regulatory T Cells Against Autoimmunity
Published on: November 8, 2016
Human urine-derived stem cells alleviate psoriasis by suppressing JAK2/STAT3 pathway-mediated macrophage polarization
You-Qiong Zhuo1,2, Qi-Ming Huang2,3, Hao-Cheng Gu2,3,4
1State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang, 330031, P. R. China.
Background:
Psoriasis is a chronic skin disease featured with aberrant keratinocyte proliferation, inflammatory cell infiltration, and immune dysregulated. Although the imbalance of M1/M2 macrophage polarization is implicated in its pathogenesis, the underlying mechanisms remain unclear. Mesenchymal stem cells exhibited potent immunomodulatory properties, representing a promising therapeutic approach for psoriasis. This study aimed to explore the role and the underlying mechanism of human urine-derived stem cells (hUSCs) in mouse psoriatic models.
Methods:
hUSCs were isolated from urine of heath volunteer and cultured in serum-free medium, and characterized by multiple approaches such as morphological analysis, biological markers examination, differentiation potentials and tumorigenicity assay. Histological analysis, immunofluorescence staining, ELISA, flow cytometry, antibody array, western blot and qRT-PCR analysis were used to assess the therapeutic effects and the underlying mechanism of hUSCs in imiquimod (IMQ)-induced mouse psoriasis models and multiple cell models.
Results:
hUSCs had the potential for self-renewal and multipotent differentiation with low immunogenicity and lacking tumorigenicity both in vitro and in vivo. Our results showed that hUSCs significantly alleviated IMQ-induced psoriasis via their paracrine, evidenced by improving morphologies, inhibiting the infiltration of macrophages, reducing the releases of the pro-inflammatory cytokines. Mechanistically, we revealed that the protective effects of hUSCs on psoriasis were involved in suppressing M1 and promoting M2 macrophage polarization, and inhibiting NETs formation through inhibiting JAK2/STAT3 pathway. Finally, we further demonstrated that hUSCs-derived TGF-β1 selectively inhibited the JAK2/STAT3 pathway-mediated the polarization of M1 and M2 macrophages to alleviate psoriasis in mouse and cellular models.
Conclusions:
Our data demonstrated that hUSCs remarkably ameliorated psoriasis by suppressing M1 and promoting M2 macrophage polarization through they-derived TGF-β1 inhibiting the JAK2/STAT3 pathway. Our results have revealed the molecular mechanism of hUSCs in treating psoriasis, highlighting a safe and effective cellular treatment method for psoriasis.
Insights
Human urine-derived stem cells (hUSCs) alleviate psoriasis by modulating macrophage polarization via TGF-β1 and JAK2/STAT3 signaling. This study reveals hUSCs as a safe and effective cellular therapy for psoriasis.
Area of Science:
- Regenerative Medicine
- Immunology
- Dermatology
Background:
- Psoriasis is a chronic skin disease characterized by immune dysregulation and aberrant keratinocyte proliferation.
- Imbalance in M1/M2 macrophage polarization is implicated in psoriasis pathogenesis, but mechanisms remain unclear.
- Mesenchymal stem cells show therapeutic potential for psoriasis due to their immunomodulatory properties.
Purpose of the Study:
- To investigate the therapeutic role of human urine-derived stem cells (hUSCs) in mouse models of psoriasis.
- To elucidate the underlying molecular mechanisms of hUSCs in treating psoriasis.
Main Methods:
- hUSCs were isolated, cultured, and characterized for differentiation potential and tumorigenicity.
- Therapeutic effects and mechanisms were assessed using imiquimod-induced mouse psoriasis models and cell models.
- Techniques included histology, immunofluorescence, ELISA, flow cytometry, antibody array, western blot, and qRT-PCR.
Main Results:
- hUSCs demonstrated self-renewal, multipotent differentiation, low immunogenicity, and lack of tumorigenicity.
- hUSCs alleviated psoriasis symptoms by inhibiting macrophage infiltration and pro-inflammatory cytokine release.
- hUSCs suppressed M1 and promoted M2 macrophage polarization via TGF-β1 inhibition of the JAK2/STAT3 pathway, also reducing NETs formation.
Conclusions:
- hUSCs effectively ameliorate psoriasis by shifting macrophage polarization from M1 to M2 through TGF-β1 mediated JAK2/STAT3 pathway inhibition.
- This study reveals a novel molecular mechanism for hUSCs in psoriasis treatment.
- hUSCs represent a promising, safe, and effective cellular therapy for psoriasis.
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