Method Profile

T-Cell-Integrated Human Skin Equivalents for Apremilast Response

Primary human skin equivalents with different CD4+ and CD8+ T-cell combinations support tissue and cytokine measurements during anti-inflammatory drug testing.

SkinEngineered Human Tissues
Original Figure 4 compares IFN-γ, IL-17A, TNF-α, IL-6 and IL-10 responses in four donor experiments.
Cytokine secretion after apremilast in skin equivalents with different T-cell combinations, normalized to each untreated condition. (Vahav et al. / Frontiers in Immunology, 2026, Fig. 4, CC BY 4.0)

Research Applications

Investigation of immune-subset and donor contributions to psoriasis-associated pharmacological responses.

Model & Design

Healthy-donor keratinocytes/fibroblasts in a full-thickness tissue combined with polarized Th1/Th17, Tc1/Tc17 or mixed T-cell populations.

Experimental Format

Three-day immune co-culture with 2.5 μM apremilast introduced at T-cell integration; secreted mediators normalized to matched untreated compositions.

Model Components

  • Component

    Human tissues

    Description

    Stratified epidermis and fibroblast-populated dermal support from healthy donor tissue.

  • Component

    Immune component

    Description

    Healthy-volunteer CD4+ and CD8+ subsets polarized into defined type 1/type 17 combinations.

  • Component

    Measurements

    Description

    Cytokine secretion, histology, differentiation markers and antimicrobial proteins.

Measurements & Endpoints

  • IFN-γ, IL-17A and TNF-α
  • IL-6 and IL-10
  • Epidermal differentiation/barrier-associated markers
  • T-cell localization

Analysis

Retain donor-level patterns and distinguish independent donor experiments from within-experiment technical triplicates.

Published Evidence

  • Study Design

    Compare subset composition with and without apremilast, alongside transferred T-cell-free controls and a non-transferred handling reference.

    Study Sample

    Four independent experiments using different skin/T-cell donors, with technical triplicates in each condition.

    Comparison

    Matched untreated cell combinations and T-cell-free skin equivalents.

    Finding

    CD4+ cultures showed cytokine-suppression trends in most donors without pooled statistical significance; CD8+ cultures were largely unresponsive. IL-6 increased across T-cell-containing donor cultures.

    Interpretation & Limits
    • The small donor panel limits statistical power.
    • The immune/vascular composition is incomplete and current throughput is limited.
    • Healthy-donor reconstructed tissues reproduce selected psoriasis-associated features rather than a complete patient skin lesion.

Sources

  1. CD4+ and CD8+ T cells contribute to psoriasis phenotype when integrated into human skin equivalents for drug testing. Frontiers in Immunology (2026). ↗