MemoryCells in Atopic Dermatitis: Paving the Way to Disease Modification Dominguez Lopez, Raquel Aranda Clemente, Carlos José Gómez de la Fuente, Enrique Pérez García, Bibiana Perez Bootello, Javier Abbad Jaime de Aragon, Carlota González Cantero, Álvaro Berna Rico, Emilio Atopic dermatitis Immunological memory Tissue-resident memory T cells Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disease in which persis tence of immunological memory underlies disease recurrence and progression toward atopic comorbidities. Evidence indicates that pathogenic tissue-resident memory T cells (TRM), including Th2- and Th22-skewed subsets, among others, persist in both lesional and clinically resolved skin and rapidly re-initiate inflammation through production of IL-4, IL-13, IL-22 and IL-31, promoting barrier dysfunction and pruritus. In parallel, circulating CLA+ memory T cells retain skin-homing capacity and contribute to flare reacti vation, while IgG1+CD23 IL-4Rα+ type-2 memory B cells (MBC2) constitute a reservoir for high-affinity IgE production, linking cutaneous inflammation with allergic comorbidities. These adaptive memory compartments are sustained by epithelial alarmins, dendritic cell–derived chemokines such as CCL17, CCL22 and CCL18, and the OX40/OX40L costim ulatory pathway, which promotes differentiation, survival and tissue retention of memory T cells. Clinical and transcriptomic studies show how, although IL-4/IL-13 blockade reduces circulating type-2 responses, Th2A cells, Tc2 cells and activated dendritic cells can persist in clinically resolved skin, providing a mechanistic basis for relapse after treatment with drawal. Together, these findings support the relevance of targeting memory-imprinting pathways as a promising mechanism to achieve durable disease modification in AD. 2026-03-04T09:30:29Z 2026-03-04T09:30:29Z 2026-03-03 journal article Dominguez-Lopez, R., Aranda, C. J., Gómez-de la Fuente, E., Pérez-García, B., Perez-Bootello, J., Abbad-Jaime de Aragon, C., González-Cantero, Á., & Berna-Rico, E. (2026). Memory Cells in Atopic Dermatitis: Paving the Way to Disease Modification. International Journal of Molecular Sciences, 27(5), 2371. https://doi.org/10.3390/ijms27052371 https://hdl.handle.net/10481/111882 10.3390/ijms27052371 eng http://creativecommons.org/licenses/by/4.0/ open access Atribución 4.0 Internacional MDPI