Methotrexate and ciclosporin both reduce levels of circulating IL-4 and IL-13 expressing CD4+ memory T-cells in childhood atopic dermatitis

Anton Olsson, Kathryn Steel, Rachael Cooper, Ashley P Jones, Kaitlyn R Chan, Graham Ogg, Alan D Irvine, Carsten Flohr, Leonie S Taams, on behalf of the TREAT trial team, Clinical and Experimental Dermatology, 2025;, llaf301, https://doi.org/10.1093/ced/llaf301

Abstract

Atopic dermatitis (AD) is a chronic dermatosis characterised by type-2 inflammatory responses, skin barrier anomalies, and microbiome dysregulation. The variation of AD presentation necessitates a better understanding of the underlying disease mechanisms and the modulation of immune markers over a treatment course. Globally the most used systemic therapies for moderate-to-severe AD are methotrexate (MTX) and ciclosporin (CyA).

Gating strategy for identification and analysis of
cytokine-expressing CD4+ T 4 cells in peripheral blood
from TREAT participants.

The TReatment of severe Atopic Eczema in children Trial (TREAT) was a randomised controlled trial assessing the efficacy and safety of methotrexate and ciclosporin. Peripheral blood samples from n=18 TREAT participants were analysed in a longitudinal immunological study with a focus on cytokine-expressing CD4+ T-cells.

The analysis showed that both MTX and CyA were associated with a decreased percentage of IL-4 and IL-13 expressing CD4+ memory T-cells, corresponding to improved disease severity. Patients receiving MTX experienced a more sustained decrease in IL-4 expressing T-cells, which corresponds to the longer-term improved disease control observed in the MTX arm.

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