A reappraisal of type 2 cytokine-producing cells in atopic dermatitis: Spotlight on Tc2 cells

Atopic dermatitis (AD) is a chronic inflammatory skin disorder driven by type 2 cytokines, particularly IL-4, IL-13, and IL-31. CD4⁺ Th2 cells have long been considered the primary producers of these cytokines in AD, but the contribution of CD8⁺ Tc2 cells has received limited attention. Recent advances in single-cell RNA sequencing, which allow for cytokine expression profiling at the single-cell level, challenge this traditional paradigm. This review reappraises the cellular sources of IL-13-a key effector cytokine in AD lesions-by not only summarizing prior studies but also reanalyzing multiple publicly available scRNA-seq datasets. These analyses indicate that Tc2 cells may represent a substantial, and in some cases dominant, source of IL-13 in lesional skin, alongside Th2 cells. This perspective invites a reconsideration of the Th2-centric model and proposes that a broader view-including Tc2 cells-is needed to fully understand type 2 immune responses in AD.