Infant skin DCs orchestrate a peripheral type-17 allergy checkpoint

A Nature study shows that in infancy, exposure to common allergens triggers a dual response: locally in the skin, peripheral immune-inducer dendritic cells (pii-DCs) activate γδ T17 cells via IL-23, initiating type 17 inflammation, while a canonical Th2 response is primed in draining lymph nodes. The pii-DC state is enabled by an immature hypothalamic–pituitary–adrenal axis with low systemic glucocorticoids; deleting the glucocorticoid receptor in DCs recapitulates this phenotype. This reveals a developmental neuroendocrine checkpoint that shapes age-specific allergen responses and primes exaggerated allergic lung inflammation upon subsequent exposures.