Peripheral immune-inducer dendritic cells drive early-life allergic inflammation.
basic_science · Level V
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- Record sourced from PubMed, PMID 41741647.
- Also identified by DOI 10.1038/s41586-026-10162-x and PMC identifier 13036635.
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Abstract
Atopic diseases associated with allergens, as well as allergic diseases, frequently arise early in life; however, the age-dependent mechanisms governing immune responses to allergens remain poorly understood<sup>1</sup>. Here we find that in early life, exposure to common allergens triggers a distinct bifurcated immune response, simultaneously triggering type 17 inflammation in the skin and initiating canonical T helper 2 sensitization in the lymph nodes. This early-life γδ type 17-mediated dermatitis primes the exaggerated allergic lung inflammation upon secondary allergen exposure. Mechanistically, we find dendritic cell (DC)-mediated type 17 activation directly in the skin without requiring migration to lymph nodes; we term this state 'peripheral immune inducer' (pii) DC. CD301b<sup>+</sup> conventional type 2 DCs acquire allergen, adopt the pii-DC state, produce IL-23 and activate local γδ type 17 cells independently of lymph-node engagement. The pii-DC state is enabled by the immature hypothalamic-pituitary-adrenal axis and physiologically low systemic glucocorticoids characteristic of early life<sup>2,3</sup>; DC-specific deletion of the glucocorticoid receptor recapitulates the pii-DC phenotype. These findings define a developmental checkpoint, set by neuroendocrine maturation, that enables in situ DC activation and immune induction, thereby shaping age-dependent responses to allergens.