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- Ilana Reznikov1,
- Abonti Nur Ahmed1,
- Ikjot Sidhu ORCID: orcid.org/0000-0002-1470-64211,
- Jill Wisnewski ORCID: orcid.org/0000-0003-2976-32312,
- Asma Farhat1,
- Aleksandr Prystupa1,
- Piotr Konieczny ORCID: orcid.org/0000-0003-4114-349X3,
- Kody Mansfield4,
- Melissa L. Cooper ORCID: orcid.org/0000-0003-4337-83565,
- Stephen T. Yeung ORCID: orcid.org/0000-0002-9710-55676,
- Madeline Kim7,
- Sophia Adeghe8,
- Katherine D. Gaines ORCID: orcid.org/0009-0005-8038-88701,
- Meredith Manson7,
- Ji Hyun Sim9,10,
- Qingrong Huang ORCID: orcid.org/0000-0002-7692-516011,
- Ata S. Moshiri ORCID: orcid.org/0000-0001-6684-450312,
- Kamal M. Khanna ORCID: orcid.org/0000-0002-9328-381713,14,
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- Emma Guttman-Yassky ORCID: orcid.org/0000-0002-9363-324X7,
- Amanda W. Lund ORCID: orcid.org/0000-0001-7389-998312,13,15,
- Niroshana Anandasabapathy8,16 &
- Shruti Naik ORCID: orcid.org/0000-0002-2216-51351,7
Nature (2026)Cite this article
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- Acute inflammation
- Conventional dendritic cells
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 understood1. 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+ 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 life2,3; 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.
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