Infant dermatitis induces long-lasting innate immune imprinting associated with the exacerbated adult atopic dermatitis-like skin inflammation

Background Atopic dermatitis (AD) frequently begins during infancy, and AD arising in early infancy represents a predictor of persistent AD. However, the mechanisms by which infantile skin inflammation programs future inflammatory susceptibility remain poorly understood.Methods Two-week-old mice were treated with MC903 (vitamin D analogue) for 2 weeks and allowed to recover until adulthood. Topical corticosteroids were administered to a subset of mice after the induction of dermatitis during infancy. At 8 weeks of age, mice were rechallenged with MC903. Skin inflammation was evaluated by ear thickness, histological analysis, quantitative PCR, and flow cytometry. IL-4 and IL-5 reporter mice were used to identify the cellular sources of type 2 cytokines, and ILC populations were analyzed by uniform manifold approximation and projection.Results MC903 application during infancy induced AD-like dermatitis with epidermal hyperplasia, increased type 2 cytokines, and infiltration of eosinophils, basophils, and ILCs. Mice experiencing infantile dermatitis developed markedly enhanced skin inflammation upon MC903 rechallenge in adulthood. Basophils were the major source of IL-4, whereas CCR6- ILCs produced IL-5. Infantile dermatitis resulted in the persistent expansion of Sca-1+CCR6- ILC populations. Notably, TSLP expression upon rechallenge was not increased in mice with a history of infantile dermatitis compared with controls. Although topical corticosteroid treatment reduced acute inflammation, it failed to prevent an exaggerated inflammatory response upon adult rechallenge.Conclusions Infantile skin inflammation establishes long-lasting innate immune imprinting that predisposes skin to exaggerated type 2 inflammation later in life. Under the condition tested, topical corticosteroid treatment did not attenuate this enhanced responsiveness.