Sustaining the T-cell activity in xenografted psoriasis skin

PLoS One. 2023 Jan 17;18(1):e0278390. doi: 10.1371/journal.pone.0278390. eCollection 2023.

Abstract

Xenografting of psoriasis skin onto immune deficient mice has been widely used to obtain proof-of-principle of new drug candidates. However, the lack of human T-cell activity in the grafts limits the use of the model. Here, we show that xenografting of lesional skin from psoriasis patients onto human IL-2 NOG mice results in increased numbers of human CD3+ cells in the grafts, axillary lymph nodes and blood from human IL-2 NOG mice compared to C.B-17 scid and NOG mice. In addition, disease relevant human cytokine levels were higher in graft lysates and serum from human IL-2 NOG mice. However, the epidermis was lacking and no efficacy of ustekinumab, a human anti-P40 antibody targeting both IL-12 and IL-23, was shown. Thus, despite the sustained T-cell activity, the model needs further investigations and validation to capture more aspects of psoriasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Humans
  • Interleukin-2*
  • Mice
  • Psoriasis* / pathology
  • Skin / pathology
  • T-Lymphocytes / pathology
  • Transplantation, Heterologous

Substances

  • Interleukin-2

Grants and funding

The funder provided support in the form of salaries for authors P.K.F.C, M.H.H.-H. and J.K. This study was also funded by LEO Pharma and Innovationsfonden (grant number 5189-00097B) awarded to P.K.F.C. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.