Frontiers in Immunology (Sep 2023)

Alleviating psoriatic skin inflammation through augmentation of Treg cells via CTLA-4 signaling peptide

  • Woo-Sung Lee,
  • Kyung-Ho Nam,
  • Jong Hoon Kim,
  • Won-Ju Kim,
  • Jeong Eun Kim,
  • Jeong Eun Kim,
  • Eui-Cheol Shin,
  • Eui-Cheol Shin,
  • Gil-Ran Kim,
  • Gil-Ran Kim,
  • Je-Min Choi,
  • Je-Min Choi,
  • Je-Min Choi,
  • Je-Min Choi

DOI
https://doi.org/10.3389/fimmu.2023.1233514
Journal volume & issue
Vol. 14

Abstract

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Psoriasis is a chronic inflammatory skin disease characterized by hyperplasia of keratinocytes and immune cell infiltration. The IL-17-producing T cells play a key role in psoriasis pathogenesis, while regulatory T (Treg) cells are diminished during psoriatic inflammation. Current psoriasis treatments largely focus on IL-17 and IL-23, however, few studies have explored therapeutic drugs targeting an increase of Treg cells to control immune homeostasis. In this study, we investigated the effects of a cytotoxic T lymphocyte antigen-4 (CTLA-4) signaling peptide (dNP2-ctCTLA-4) in Th17, Tc17, γδ T cells, Treg cells in vitro and a mouse model of psoriasis. Treatment with dNP2-ctCTLA-4 peptide showed a significant reduction of psoriatic skin inflammation with increased Treg cell proportion and reduced IL-17 production by T cells, indicating a potential role in modulating psoriatic skin disease. We compared dNP2-ctCTLA-4 with CTLA-4-Ig and found that only dNP2-ctCTLA-4 ameliorated the psoriasis progression, with increased Treg cells and inhibited IL-17 production from γδ T cells. In vitro experiments using a T cell-antigen presenting cell co-culture system demonstrated the distinct mechanisms of dNP2-ctCTLA-4 compared to CTLA-4-Ig in the induction of Treg cells. These findings highlight the therapeutic potential of dNP2-ctCTLA-4 peptide in psoriasis by augmenting Treg/Teff ratio, offering a new approach to modulating the disease.

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