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Objective <p>Psoriasis is a chronic inflammatory skin disease characterized by recurrent exacerbations and remissions, driven by genetic, environmental, and external factors such as mechanical stress and skin dryness. This study aimed to uncover a novel pathogenic mechanism underlying psoriasis involving splicing factor proline- and glutamine-rich protein/ calgranulin A (SFPQ/S100A8) complex formation.</p> Methods <p>We utilized a well-characterized IMQ-induced psoriasis-like mouse model and analyzed keratinocytes isolated from mouse skin tissues to assess the correlation between the SFPQ/S100A8 complex and disease severity. In human epidermal keratinocytes (HaCaT), IMQ treatment enhanced chromosome region maintenance 1 (CRM1) activation, leading to the cytoplasmic translocation of SFPQ and subsequent formation of the SFPQ/S100A8 complex. The effects of leptomycin B (LMB), a CRM1 inhibitor, on these processes were also evaluated.</p> Results <p>Time-dependent administration of IMQ enhanced Psoriasis Area and Severity Index (PASI) scores and serum cytokines such as tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-17, and IL-22 in the mice. After the onset of psoriasis in the mice, SFPQ bound to S100A8 in the cytoplasm of keratinocytes, resulting in the formation of the SFPQ/S100A8 complex. The complex was positively correlated with PASI scores and serum cytokines, and negatively associated with filaggrin expression. In HaCaT cells, IMQ treatment enhanced CRM1-mediated nuclear export, leading to the cytoplasmic translocation of SFPQ and subsequent formation of the SFPQ/S100A8 complex. Treatment with LMB reduced SFPQ cytoplasmic translocation and inhibited SFPQ/S100A8 complex formation. Moreover, treatment with LMB significantly decreased the secretion of IFN-γ, IL-17, and IL-22 and restored filaggrin expression.</p> Conclusion <p>CRM1-mediated SFPQ/S100A8 complex formation may contribute to psoriasis pathogenesis by promoting T helper 1/T helper 17 hybrid (Th1/17) cytokine expression and filaggrin downregulation.</p>

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Role of CRM1-mediated SFPQ/S100A8 complex formation in psoriasis

  • 期刊论文

  • 发表日期：

    2026年4月21日

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  • Geunyeong Kim,
  • Yujin Hong,
  • Ji-Sook Lee,
  • Juram Lee,
  • Tae Young Han,
  • In Sik Kim

摘要

Objective

Psoriasis is a chronic inflammatory skin disease characterized by recurrent exacerbations and remissions, driven by genetic, environmental, and external factors such as mechanical stress and skin dryness. This study aimed to uncover a novel pathogenic mechanism underlying psoriasis involving splicing factor proline- and glutamine-rich protein/ calgranulin A (SFPQ/S100A8) complex formation.

Methods

We utilized a well-characterized IMQ-induced psoriasis-like mouse model and analyzed keratinocytes isolated from mouse skin tissues to assess the correlation between the SFPQ/S100A8 complex and disease severity. In human epidermal keratinocytes (HaCaT), IMQ treatment enhanced chromosome region maintenance 1 (CRM1) activation, leading to the cytoplasmic translocation of SFPQ and subsequent formation of the SFPQ/S100A8 complex. The effects of leptomycin B (LMB), a CRM1 inhibitor, on these processes were also evaluated.

Results

Time-dependent administration of IMQ enhanced Psoriasis Area and Severity Index (PASI) scores and serum cytokines such as tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-17, and IL-22 in the mice. After the onset of psoriasis in the mice, SFPQ bound to S100A8 in the cytoplasm of keratinocytes, resulting in the formation of the SFPQ/S100A8 complex. The complex was positively correlated with PASI scores and serum cytokines, and negatively associated with filaggrin expression. In HaCaT cells, IMQ treatment enhanced CRM1-mediated nuclear export, leading to the cytoplasmic translocation of SFPQ and subsequent formation of the SFPQ/S100A8 complex. Treatment with LMB reduced SFPQ cytoplasmic translocation and inhibited SFPQ/S100A8 complex formation. Moreover, treatment with LMB significantly decreased the secretion of IFN-γ, IL-17, and IL-22 and restored filaggrin expression.

Conclusion

CRM1-mediated SFPQ/S100A8 complex formation may contribute to psoriasis pathogenesis by promoting T helper 1/T helper 17 hybrid (Th1/17) cytokine expression and filaggrin downregulation.